ascorbic-acid and Carcinoma--Squamous-Cell

China has some of the highest incidence rates for gastric adenocarcinoma (GA) and esophageal squamous cell carcinoma (ESCC) in the world. Prospective studies suggested that vitamin C may reduce risks; however, associations are unclear because of limited sample size.. The objective was to examine the relation between prediagnostic plasma vitamin C and the risk of GA and ESCC.. A case-cohort study was used to assess the association between prediagnostic plasma vitamin C and incidence of GA (n = 467) and ESCC (n = 618) in the General Population Nutrition Intervention Trial. With the use of multivariate Cox proportional hazards models, we estimated the HRs and 95% CIs. We also conducted a meta-analysis of the literature up to 1 October 2012 on the relation between circulating vitamin C and gastric cancer incidence. Two cohort studies and the current study were included to assess the body of evidence.. For GA, each 20-μmol/L increase in plasma vitamin C was associated with a 14% decrease in risk (HR: 0.86; 95% CI: 0.76, 0.96). Compared with individuals with low plasma vitamin C concentrations (≤28 μmol/L), those with normal concentrations (>28 μmol/L) had a 27% reduced risk of GA (HR: 0.73; 95% CI: 0.56, 0.94). No association between vitamin C concentrations and ESCC was seen. Meta-analysis showed that the risk of incident GA among those with the highest concentration of plasma vitamin C was 31% lower (random-effects-pooled-odds ratio 0.69; 95% CI: 0.54, 0.89) than those in the lowest category.. Our data provide evidence that higher circulating vitamin C was associated with a reduced risk of incident GA, but no association was seen for ESCC.

Topics: Ascorbic Acid; Asian People; Carcinoma, Squamous Cell; China; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Humans; Incidence; Odds Ratio; Proportional Hazards Models; Prospective Studies; Risk Factors; Stomach Neoplasms

Squamous cell carcinoma of the oral cavity has long been seen as an attractive candidate for chemoprevention strategies. Because of the poor out-comes associated with the disease, the presence of identifiable premalignant lesions, and the failure of local preventive therapies, such as surgery, many investigators have hoped to find an effective chemopreventive compound. Initial enthusiasm surrounding high-dose retinoids gave way to concerns regarding toxicity and short duration of response. Although many of the other agents discussed above have shown promise, as yet none have been proven safe and effective in large-scale randomized trials. Much has been learned,however, about the molecular process of oral carcinogenesis from studies of these agents. Ongoing and future studies of chemopreventive agents in oral cancer hopefully will be able to exploit our expanding knowledge of these molecular pathways.

Topics: Antineoplastic Agents; Ascorbic Acid; Carcinoma, Squamous Cell; Drugs, Chinese Herbal; Flavonoids; Folic Acid; Humans; Mouth Neoplasms; Precancerous Conditions; Retinoids; Selenium; Vitamin A; Vitamin E

Among individuals with a history of head and neck cancer and tobacco abuse the risk of second primary cancers in the upper aerodigestive tract is high. Chemoprevention of oral squamous cell carcinomas is based on two conditions: Premalignant mucosa lesions are treated with chemopreventive agents in order to prevent malignant conversion (primary prevention). In secondary prevention of oral cancer, after curative therapy patients are treated by chemoprevention in order to reduce the rate of second primaries. This paper presents a comprehensive clinical review of oral cancer prevention studies, highlighting the agents mostly used, such as beta-carotene, alpha-tocopherol, ascorbic acid, and retinoids. Although most intervention trials showed good overall response with these substances, high relapse rates and serious side effects, in most cases related to the retinoid compounds were noticed. In addition, in all prospective randomized chemoprevention trials (CARET, ATBC and PHS) no significant evidence of benefit for supplementation with alpha-tocopherol, beta-carotene or retinyl palmitate was reported.

Topics: Antineoplastic Agents; Ascorbic Acid; Carcinoma, Squamous Cell; Carotenoids; Chemoprevention; Head and Neck Neoplasms; Humans; Mouth Neoplasms; Neoplasms, Second Primary; Retinoids; Treatment Outcome; Vitamin E

Experimental animal studies have unambiguously demonstrated that topical sunscreens can prevent squamous cell carcinoma and photoaging (damage of collagen and elastic fibers of the skin). Although data from clinical studies and surrogate markers also indicate such photoprotective effects in man, there is a lack of controlled, prospective clinical trials to provide definite evidence in man. Because of inadequate data, no definite conclusions can be drawn about the cancer-preventive activity of topical use of sunscreens against basal cell carcinoma and malignant melanoma.

Topics: Administration, Topical; Adult; Animals; Antioxidants; Ascorbic Acid; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Disease Models, Animal; Humans; Melanoma; Mice; Mice, Hairless; Neoplasms, Radiation-Induced; Prospective Studies; Randomized Controlled Trials as Topic; Skin Aging; Skin Neoplasms; Sunscreening Agents; Time Factors; Ultraviolet Rays; Vitamin E

Cervix carcinoma is an important health problem world-wide, being the second most common cancer among women, ranking first in many developing countries. A number of important epidemiological risk factors have been identified as contributing to the development of CIN and invasive cervix carcinoma. Of key importance is infection with human papillomavirus (HPV), which is the primary risk factor. There are evolving primary and secondary preventive strategies that could further reduce the burden from cervical carcinoma. The possible primary preventive strategies include risk reduction, diet or dietary supplements, HPV vaccines, and other chemopreventive agents. The possible advances in secondary preventive strategies include new technologies for Pap smears, HPV typing triage, and other adjuvant screening procedures. The impact of these strategies will depend upon evidence to support their use along with the characteristics of the population and environment in which they are used.

Topics: Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; beta Carotene; Carcinoma, Squamous Cell; Clinical Trials as Topic; Colposcopy; Diet; Female; Folic Acid; Humans; Image Processing, Computer-Assisted; Mass Screening; Nutritional Requirements; Papanicolaou Test; Papillomaviridae; Papillomavirus Infections; Photochemotherapy; Risk Factors; Tumor Virus Infections; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vaginal Smears; Viral Vaccines; Vitamin E; Vitamins

L-ascorbic acid is an essential dietary vitamin in humans, primates and certain mammals and is endogenously synthesised in some species. Epidemiological and ecological studies have shown that L-ascorbic acid has a protective effect against cancer, in particular non-hormone-dependent malignancies, such as oropharyngeal neoplasms. Experimental in vivo and in vitro studies, however, have yielded more controversial results, suggesting that the effects of L-ascorbic acid are dose- and perhaps, time-dependent with different effects depending on the species or organ studied. An update of the epidemiological and experimental evidence linking L-ascorbic acid to oral cancer and carcinogenesis is discussed together with a brief review of the possible mechanisms of action of L-ascorbic acid.

Topics: Animals; Ascorbic Acid; Carcinogenicity Tests; Carcinogens; Carcinoma, Squamous Cell; Dose-Response Relationship, Drug; Female; Humans; Male; Mouth Neoplasms; Research Design; Species Specificity

Epidemiologic investigations have been instrumental in identifying numerous factors associated with the development of cancer. Tobacco and alcohol are unquestionably the major risk factors for squamous cell carcinoma of the head and neck region. Diet appears to play a role in the development of these cancers, as nutritional deficiencies have been found to increase risk. Clinical observation and epidemiologic studies have also identified ionizing radiation as an unequivocal risk factor, although of lesser importance from the public health point of view. Overall, epidemiologic evidence shows that occupational exposures play a minor, though definite, role in the development of head and neck cancer. For sinonasal cancer, however, studies corroborate that occupational exposures are the major determinants of disease.

Topics: Ascorbic Acid; Carcinoma, Squamous Cell; Ethanol; Fruit; Head and Neck Neoplasms; Humans; Neoplasms, Radiation-Induced; Occupational Diseases; Risk; Smoking; United States; Vegetables; Vitamin A

The incidence of adenocarcinoma of the esophagus is increasing in most Western industrialized nations especially in white males. The impact of vitamins on the development of squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus has not been elucidated. The goal of this pilot-study was to analyze the influence of daily vitamin consumption on the frequency of esophageal carcinoma in Germany.. Ninety-nine patients (males) with esophageal carcinoma (52 with SCC and 47 with AC) were compared to a control group of 50 randomly selected males from the Cologne area. Using a computer program to record the data, patients and controls were questioned in detail about their dietary habits. The interaction between known risk factors and the influence of vitamins on esophageal tumor risk were analyzed using logistic regression analysis.. The univariate analysis showed a significant risk reduction with increased intake of beta-carotene, vitamin C, vitamin E, and folic acid for both AC and for SCC. The results of logistic regression analysis were compatible with the known risk factors for SCC (alcohol and tobacco) and for AC (obesity, tobacco, and alcohol) and showed a significant risk reduction with an intake of vitamin E greater than 13 mg/day (RR=0.13, 95% CI=0.1-0.5, P=0.0004) and vitamin C greater than 100 mg/day (RR=0.33, 95% CI=0.11-0.92, P=0.034) for patients with SCC and similar results for patients with AC.. Our data showed that low intake of vitamin C and E correlates significantly with the development of squamous cell carcinoma as well as adenocarcinoma of the esophagus in males. The relevance of interaction of vitamins with other dietary factors, alcohol, and tobacco are topics of current research.

Topics: Adenocarcinoma; Adult; Alcohol Drinking; Ascorbic Acid; Body Mass Index; Carcinoma, Squamous Cell; Case-Control Studies; Dietary Supplements; Esophageal Neoplasms; Folic Acid; Germany; Humans; Incidence; Male; Pilot Projects; Risk Factors; Smoking; Surveys and Questionnaires; Vitamin A; Vitamin E

Topics: Ascorbic Acid; Carcinoma, Squamous Cell; Humans; Risk Factors; Skin Neoplasms

Oral squamous cell carcinoma (OSCC) can arise anywhere in the oral cavity. OSCC's molecular pathogenesis is complex, resulting from a wide range of events that involve the interplay between genetic mutations and altered levels of transcripts, proteins, and metabolites. Platinum-based drugs are the first-line treatment for OSCC; however, severe side-effects and resistance are challenging issues. Thus, there is an urgent clinical need to develop novel and/or combinatory therapeutics. In this study, we investigated the cytotoxic effects of pharmacological concentrations of ascorbate on two human oral cell lines, the oral epidermoid carcinoma meng-1 (OECM-1) cell and the Smulow-Glickman (SG) human normal gingival epithelial cell. Our study examined the potential functional impact of pharmacological concentrations of ascorbates on the cell-cycle profiles, mitochondrial-membrane potential, oxidative response, the synergistic effect of cisplatin, and the differential responsiveness between OECM-1 and SG cells. Two forms of ascorbate, free and sodium forms, were applied to examine the cytotoxic effect and it was found that both forms had a similar higher sensitivity to OECM-1 cells than to SG cells. In addition, our study data suggest that the determinant factor of cell density is important for ascorbate-induced cytotoxicity in OECM-1 and SG cells. Our findings further revealed that the cytotoxic effect might be mediated through the induction of mitochondrial reactive oxygen species (ROS) generation and the reduction in cytosolic ROS generation. The combination index supported the agonistic effect between sodium ascorbate and cisplatin in OECM-1 cells, but not in SG cells. In summary, our current findings provide supporting evidence for ascorbate to serve as a sensitizer for platinum-based treatment of OSCC. Hence, our work provides not only repurposing of the drug, ascorbate, but also an opportunity to decrease the side-effects of, and risk of resistance to, platinum-based treatment for OSCC.

Topics: Antineoplastic Agents; Apoptosis; Ascorbic Acid; Carcinoma, Squamous Cell; Cell Line, Tumor; Cisplatin; Humans; Mouth Neoplasms; Oxidative Stress; Reactive Oxygen Species

Topics: Ascorbic Acid; Carcinoma, Squamous Cell; Cell Line, Tumor; Eating; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; MicroRNAs; Squamous Cell Carcinoma of Head and Neck; Sugars; Vitamins

The genetic features of primary lymphoepithelioma-like carcinoma (LELC) of the upper urinary tract have not been systematically explored. In this study, tumor mutation profiling was performed using whole-genome sequencing in two patients with LELC of the renal pelvis. Novel candidate variants relevant to known disease genes were selected using rare-variant burden analysis. Subsequently, a population-based study was performed using the Surveillance, Epidemiology, and End Results (SEER), PubMed, MEDLINE, Embase, and Scopus databases to explore clinical features and prognostic risk factors. Immunohistochemical analysis revealed seven positive cytokeratin-associated markers in tumor cells and five positive lymphocyte-associated markers in and around the tumor area. Sub-sequently, we identified KDM6A as the susceptibility gene and LEPR as the driver gene by Sanger sequencing in case 2 of LELC of the renal pelvis. Three mutation sites of the existing targeted drugs were screened: CA9, a therapeutic target for zonisamide; ARVCF, a therapeutic target for bupropion; and PLOD3, a therapeutic target for vitamin C. In a population-based study, patients with primary LELC of the upper urinary tract had clinical outcomes similar to those of patients with primary upper urinary tract urothelial carcinoma (UUT-UC) before and after propensity score matching at 1 : 5. Focal subtype was an independent prognostic factor for the overall survival of patients with LELC of the upper urinary tract. The carcinogenesis of primary LELC may be due to different genetic variations, including single-nucleotide variants, insertion and deletions, structural variations, and repeat regions, which may provide the basis for clinical diagnosis and treatment. The prognosis of LELC in the upper urinary tract is similar to that of UUT-UC. We suggest that the focal subtype can serve as a prognostic factor for LELC of the upper urinary tract; however, further studies are required to confirm this.

Topics: Ascorbic Acid; Bupropion; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Histone Demethylases; Humans; Keratins; Kidney Pelvis; Nucleotides; Prognosis; Urinary Bladder Neoplasms; Zonisamide

Topics: Antineoplastic Agents; Ascorbic Acid; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colloids; Esophageal Neoplasms; Humans; Hydrogen; Nanocomposites; Platinum; Water

A combination of metabolic modifications by light stimulus and photodynamic action is very attractive. Photobiomodulation therapy (PBMT) comprehends a vast range of applications and has been shown to be suitable to ease morbidities caused by chemotherapy and radiation, such as mucositis and dermatitis. The current study investigates the effects of near-infrared PBMT combined with porphyrin-based photodynamic therapy (PDT) in squamous cell carcinoma cell lines SCC-25 and SCC-4. The aim is to evaluate the potential of this combination to improve PDT outcome by increasing cell toxicity. Many techniques were used to verify the combined effect. Photobiomodulation (PBM) enhanced PDT action in SCC-25 cells by increasing photosensitizer (PS) uptake and production of reactive oxygen species (ROS). The equivalent was not seen in SCC-4 cells compared to the PDT only group. We believe these effects are strongly related to the interval of application between PBMT, PS incubation and PDT. Additionally, the effect of ascorbic acid on preventing PBM effects in PDT shows that ROS play an important role in the early mechanisms of PBM-PDT. Therefore, we believe PBM-PDT combination is worth exploring, for its benefit-cost ratio and simple protocols, along with the possibility of improvement in treatment resuts.

Topics: Antioxidants; Ascorbic Acid; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Cell Survival; Humans; Light; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species; Squamous Cell Carcinoma of Head and Neck

Ascorbic acid induces apoptosis, autophagy, and necrotic cell death in cancer cells. We investigated the mechanisms by which ascorbic acid induces death in laryngeal squamous cell carcinoma Hep2 cells. Ascorbic acid markedly reduced cell viability and induced death without caspase activation and an increase in cytochrome c. Hep2 cells exposed to ascorbic acid exhibited membrane rupture and swelling, the morphological characteristics of necrotic cell death. The generation of reactive oxygen species (ROS) was increased in Hep2 cells treated with ascorbic acid, and pretreatment with N-acetylcysteine blocked ascorbic acid-induced cell death. Ascorbic acid also stimulated protein kinase C (PKC) signaling, especially PKC α/β activation, and subsequently increased cytosolic calcium levels. However, ascorbic acid-induced necrotic cell death was inhibited by Ro-31-8425 (PKC inhibitor) and BAPTA-AM (cytosolic calcium-selective chelator). ROS scavenger NAC inhibited PKC activation induced by ascorbic acid and Ro-31-8425 suppressed the level of cytosolic calcium increased by ascorbic acid, indicating that ROS is represented as an upstream signal of PKC pathway and PKC activation leads to the release of calcium into the cytosol, which ultimately regulates the induction of necrosis in ascorbic acid-treated Hep2 cells. These data demonstrate that ascorbic acid induces necrotic cell death through ROS generation, PKC activation, and cytosolic calcium signaling in Hep2 cells. J. Cell. Physiol. 232: 417-425, 2017. © 2016 Wiley Periodicals, Inc.

Topics: Apoptosis; Ascorbic Acid; Calcium; Calcium Signaling; Carcinoma, Squamous Cell; Cell Line, Tumor; Enzyme Activation; Humans; Laryngeal Neoplasms; Necrosis; Protein Kinase C; Reactive Oxygen Species

The objectives of this study are to analyze oxidative DNA and lipid damage using salivary 8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and vitamins C and E in oral lichen planus lesions, oral leukoplakia, oral submucous fibrosis, oral squamous cell carcinoma (SCC), and controls and to determine the value of salivary biomarkers in the diagnosis of oral pre-cancer and cancer patients.. Unstimulated saliva was collected from a group of patients diagnosed with 40 oral squamous cell carcinoma (OSCC), 40 oral lichen planus lesions, 40 oral leukoplakia, 40 oral submucous fibrosis, and from a control group of healthy age- and gender-matched individuals. Salivary 8-OHdG, MDA, and vitamins C and E were measured.. Squamous cell carcinoma and pre-cancer patients showed significantly higher levels of salivary 8-OHdG and MDA and lower levels of vitamins C and E when compared to levels in healthy normal subjects. The specificity and sensitivity of the combination of 8-OHdG, MDA, vitamin C, and vitamin E are high for the diagnosis of oral pre-cancer and SCC compared to an individual biomarker approach using either 8-OHdG, MDA, or vitamin C and vitamin E independently.. This study indicates the presence of oxidative DNA and lipid damage in pre-cancerous and SCC patients. It is postulated that the mechanism may have a significant link to carcinogenesis in oral cancer. Detection of salivary 8-OHdG, MDA, vitamin C, and vitamin E can act as suitable diagnostic biomarkers of oral pre-cancer and cancer.. Of clinical importance is that salivary 8-OHdG, MDA, vitamin C, and vitamin E could play a significant role in oral cancer and pre-cancer patients and could therefore be useful for diagnosis in patients with oral lichen planus lesions, oral leukoplakia, oral submucous fibrosis, and oral squamous cell carcinoma.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Ascorbic Acid; Biomarkers; Biopsy; Carcinoma, Squamous Cell; Case-Control Studies; Deoxyguanosine; Female; Free Radicals; Humans; Leukoplakia, Oral; Lichen Planus, Oral; Male; Malondialdehyde; Middle Aged; Mouth Neoplasms; Oral Submucous Fibrosis; Precancerous Conditions; Risk Factors; Saliva; Sensitivity and Specificity; Vitamin E

Low-molecular-weight antioxidants are some of the most efficient agents of the skin defense mechanism against environmental factors, such as cosmic rays, smoke, and pollutants. The total skin concentrations of hydrophilic ascorbic and uric acids, as well as lipophilic α-tocopherol, β-carotene, and ubiquinol-10 antioxidants were determined by an HPLC-EC detector from 18 biopsies of human nonmelanoma skin carcinomas and 18 biopsies from skin areas adjacent to carcinomas. No significant differences in the concentrations of lipophilic antioxidants in both carcinomas and normal-looking skin areas adjacent to carcinomas were observed. On the contrary, ascorbic and uric acid concentrations were found to be 18 and 36% lower in carcinomas than in normal-looking skin areas, respectively. No statistical significance was observed between antioxidant concentrations and age, sex, phototype, profession, site of tumor, frequency, and time of UV light exposure either. Accordingly the antioxidant concentrations in both cancerous skin and adjacent normal-looking areas were found to be much higher than in normal skin, in contrast to literature data.

Topics: Adult; Aged; Aged, 80 and over; alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Humans; Male; Middle Aged; Molecular Weight; Skin; Skin Neoplasms; Ubiquinone; Uric Acid

The mainstay of the treatment of head and neck squamous cell carcinoma (HNSCC) is radiotherapy, which acts by producing free radicals. Therefore, this study was planned to observe the effect of radiotherapy on oxidative stress in patients of HNSCC.. This study was conducted on 50 histopathologically proven cases of HNSCC. The levels of nitric oxide, glutathione-S-transferase, and vitamin C were estimated colorimetrically before and after treatment in patients and in 30 age- and sex-matched healthy controls. The results were compared statistically.. The levels of nitric oxide and glutathione-S-transferase were significantly higher in patents as compared to controls and increased significantly after treatment. Vitamin C levels were significantly lower in patients as compared to controls and decreased significantly after treatment.. HNSCC leads to increased oxidative stress and treatment in the form of radiotherapy itself produces an accentuation of this stress.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Carcinoma, Squamous Cell; Case-Control Studies; Female; Glutathione Transferase; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Staging; Nitric Oxide; Squamous Cell Carcinoma of Head and Neck; Young Adult

Some dietary factors could be involved as cofactors in cervical carcinogenesis, but evidence is inconclusive. There are no data about the effect of fruits and vegetables intake (F&V) on cervical cancer from cohort studies. We examined the association between the intake of F&V and selected nutrients and the incidence of carcinoma in situ (CIS) and invasive squamous cervical cancer (ISC) in a prospective study of 299,649 women, participating in the European Prospective Investigation into Cancer and Nutrition study. Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CI). A calibration study was used to control measurement errors in the dietary questionnaire. After a mean of 9 years of follow-up, 253 ISC and 817 CIS cases were diagnosed. In the calibrated model, we observed a statistically significant inverse association of ISC with a daily increase in intake of 100 g of total fruits (HR 0.83; 95% CI 0.72-0.98) and a statistically nonsignificant inverse association with a daily increase in intake of 100 g of total vegetables (HR 0.85: 95% CI 0.65-1.10). Statistically nonsignificant inverse associations were also observed for leafy vegetables, root vegetables, garlic and onions, citrus fruits, vitamin C, vitamin E and retinol for ISC. No association was found regarding beta-carotene, vitamin D and folic acid for ISC. None of the dietary factors examined was associated with CIS. Our study suggests a possible protective role of fruit intake and other dietary factors on ISC that need to be confirmed on a larger number of ISC cases.

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Carcinoma; Carcinoma, Squamous Cell; Diet; Europe; Female; Folic Acid; Follow-Up Studies; Fruit; Humans; Middle Aged; Neoplasm Invasiveness; Nutrition Surveys; Prospective Studies; Risk Factors; Uterine Cervical Neoplasms; Vegetables; Vitamin A; Vitamin D; Vitamin E

Three Chinese herbal extracts of Drynaria baronii, Angelica sinensis and Cornus officinalis Sieb. et Zucc (referred to as DB, AS, CO, respectively) were investigated for their antitumor potential. These extracts showed very weak cytotoxicity against all nine cultured human cells (normal and tumor cells), but with some tumor-specific cytotoxicity displayed by DB and CO. These extracts showed little or no growth stimulation effects at lower concentrations (so-called 'hormetic effect'). Human oral squamous cell carcinoma cell lines (HSC-2, NA) were relatively resistant to committing apoptosis, as compared with human promyelocytic leukemia HL-60 cells. Electron-spin resonance spectroscopy shows that DB and CO scavenged superoxide anion (generated by hypoxanthine and xanthine oxidase reaction) and hydroxyl radical (generated by Fenton reaction) more efficiently than AS. DB and CO, but not AS, produced broad radical peak(s) and enhanced the superoxide scavenging activity of vitamin C. However, none of the extracts clearly enhanced the cytotoxicity of mitoxantrone, an anthracycline antitumor antibiotic. DB, but not CO and AS, showed weak anti-HIV activity. These data demonstrate several unique antitumor properties of DB.

Topics: Anti-HIV Agents; Antineoplastic Agents; Antioxidants; Apoptosis; Ascorbic Acid; Carcinoma, Squamous Cell; Cell Line, Tumor; Electron Spin Resonance Spectroscopy; Free Radical Scavengers; HL-60 Cells; Humans; Mouth Mucosa; Mouth Neoplasms; Phytotherapy; Plant Extracts; Superoxides

Head and neck squamous cell carcinomas (HNSCCs) are known for their aggressive growth and propensity to metastasize. The authors investigated the effect of a novel nutrient mixture (NM) containing ascorbic acid, lysine, proline, and green tea extract on human HNSCC cell line FaDu in vivo and in vitro. Athymic male nude mice (n = 12) were inoculated with 3 x 10(6) FaDu cells subcutaneously and randomly divided into 2 groups: group A was fed a regular diet and group B a regular diet supplemented with 0.5% NM. Four weeks later, the mice were sacrificed and their tumors were excised, weighted, and processed for histology. In vitro, FaDu cells were cultured in Dulbecco's modified Eagle's medium and exposed to NM at 0 to 1000 microg/mL in triplicate. Cell proliferation was assessed by MTT assay, matrix metalloproteinase (MMP) secretion by gelatinase zymography, invasion through Matrigel, apoptosis by live-green caspases, and cell morphology by hematoxylin-eosin staining. NM inhibited the growth of tumors by 55% (P = .0002) and exhibited dose-dependent toxicity on FaDu cells in vitro, with 53% (P = .0003) at 1000 microg/mL NM. Zymography revealed MMP-2 and phorbol 12-myristate 13-acetate-induced MMP-9 secretion. NM inhibited secretion of both MMPs in a dose-dependent manner, with virtual total inhibition at 1000 microg/mL. NM significantly inhibited FaDu invasion through Matrigel with total block at 1000 microg/mL. NM induced dose-dependent apoptosis. In conclusion, NM has therapeutic potential in the treatment of HNSCC by significantly suppressing tumor growth and significantly inhibiting MMP secretion and invasion of HNSCC cells in vitro.

Topics: Administration, Oral; Amino Acids; Animals; Apoptosis; Ascorbic Acid; Camellia sinensis; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Survival; Complementary Therapies; Food; Head and Neck Neoplasms; Humans; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Nude; Neoplasm Invasiveness; Plant Extracts; Tetradecanoylphorbol Acetate; Xenograft Model Antitumor Assays

Gefitinib is an orally active, selective epidermal growth factor receptor-tyrosine kinase inhibitor. The present study was aimed at evaluating the antitumor activity of gefitinib alone or in combination with other antitumor agents. Gefitinib showed higher cytotoxicity against five human tumor cell lines (HSC-2, HSC-3, HSC-4, T98G and U87MG) than against three human normal oral cells (gingival fibroblast HGF, pulp cell HPC and periodontal ligament fibroblast HPLF). Gefitinib showed little or no growth stimulation effects at lower concentrations (so-called hormetic effect). Non-cytotoxic concentration of gefitinib effectively enhanced the cytotoxicity of docetaxel against HSC-2 and T98G cell, but failed to enhance the cytotoxicity of other antitumor agents (mitoxantrone, doxorubicin, methotrexate, cisplatin, sodium ascorbate, sodium fluoride) or herbal extracts (Drynaria baronii, Angelica sinensis and Cornus officinalis Sieb. et Zucc). Gefitinib alone and combined with docetaxel induced internucleosomal DNA fragmentation and caspase-3 activation in human promyelocytic leukemia HL-60 cells, but not in HSC-2 or T98G cells. Combination treatment with gefitinib and docetaxel induced the formation of acidic organelles (stained with acridine orange) and mitochondrial shrinkage, vacuolization and production of autophagosome and the loss of cell surface microvilli, without destruction of cell surface and nuclear membranes in HSC-2 and T98G cells (demonstrated by transmission electron microscopy), suggesting the induction of autophagy in HSC-2 and T98G cells.

Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Ascorbic Acid; Autophagy; Carcinoma, Squamous Cell; Caspase 3; Cisplatin; Doxorubicin; Drug Screening Assays, Antitumor; Drug Therapy, Combination; Gefitinib; HL-60 Cells; Humans; Methotrexate; Mitoxantrone; Mouth; Mouth Neoplasms; Phytotherapy; Plant Extracts; Quinazolines; Sodium Fluoride; Tumor Cells, Cultured

Combined treatment with sodium nitrite (NaNO2) and ascorbic acid (AsA) has already been shown to promote rat forestomach carcinogenesis, possibly due to nitric oxide generation under acidic conditions. We hypothesized that a similar effect might occur in the esophagus when the luminal pH is decreased by acid reflux. To clarify this possibility, reflux esophagitis model rats (F344 male) were coadministered 0.2% NaNO2 in the drinking water and 1% AsA in the diet. After 32 weeks of the combined treatment, a significant increase in the incidence of epithelial hyperplasias of the lower-middle and lowest parts of the esophagus were observed compared with the basal-diet group, along with exacerbation of dysplasia and extension of the lesions. Additionally, one squamous cell papilloma was found only in the combined-treatment group. Subsequently, we confirmed the enhancing effects of NaNO2 and AsA cotreatment in the rat N-bis(2-hydroxypropyl)nitrosamine-initiated esophageal tumorigenesis model. The incidence of hyperplasia was enhanced in all segments, along with the incidence and multiplicity of squamous cell papillomas in the lowest segment of the esophagus. Thus, the data demonstrate that combined treatment with NaNO2 and AsA exerts promoting effects on rat esophageal carcinogenesis under acid reflux conditions, as in the forestomach. These findings suggest that the risk of excessive intake of a combination of nitrite and antioxidants for esophageal carcinogenesis is appreciable, particularly in patients with reflux esophagitis.

Topics: Animals; Antioxidants; Ascorbic Acid; Carcinoma, Squamous Cell; Cocarcinogenesis; Disease Models, Animal; Esophageal Neoplasms; Esophagitis, Peptic; Food Preservatives; Male; Rats; Rats, Inbred F344; Sodium Nitrite

We investigated the relationships between intakes of selected dietary nutrients and food groups and risk of cervical cancer in a hospital-based, case-control study including 239 cases diagnosed with squamous cell carcinoma of the cervix and 979 hospital patients with nonneoplastic diagnoses who completed a self-administered questionnaire between 1982 and 1998 at Roswell Park Cancer Institute. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression adjusting for age, education, smoking status, use of oral contraceptives, barrier contraceptives and spermicides, family history of cervical cancer, year questionnaire completed, and energy intake. Significant reductions in risk of approximately 40-60% were observed for women in the highest vs. lowest tertiles of dietary fiber (OR=0.59, 95% CI=0.37-0.94), vitamin C (OR=0.52, 95% CI=0.33-0.80), vitamin E (OR=0.44, 95% CI=0.27-0.72), vitamin A (OR=0.47, 95% CI=0.30-0.73), alpha-carotene (OR=0.41, 95% CI=0.27-0.63), beta-carotene (OR=0.44, 95% CI=0.29-0.68), lutein (OR=0.51, 95% CI=0.33-0.79), folate (OR=0.55, 95% CI=0.34-0.88), and total fruit and vegetable intake (OR=0.52, 95% CI=0.34-0.77). Our findings suggest that a diet rich in plant-based nutrients may be important in reducing the risk of cervical cancer.

Topics: Ascorbic Acid; Carcinoma, Squamous Cell; Carotenoids; Case-Control Studies; Confidence Intervals; Diet; Dietary Fiber; Female; Folic Acid; Fruit; Humans; Logistic Models; Menopause; Middle Aged; Odds Ratio; Risk Factors; Surveys and Questionnaires; Uterine Cervical Neoplasms; Vegetables; Vitamin A; Vitamin E

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) can function both as initiators and promoters in carcinogenesis. Antioxidants provide protection against cellular and molecular damage caused by ROS and RNS. We conducted a study to evaluate the levels of lipid peroxidation products, nitric oxide (NO) products and antioxidants in patients with head and neck squamous cell carcinoma (HNSCC). Fifty one HNSCC patients, 33 healthy tobacco smokers/chewers as tobacco user controls, and 37 non-smokers/chewers as normal controls were recruited for this study. Lipid peroxidation products, NO products and antioxidants were measured using spectrophotometric methods. Lipid peroxidation products, including lipid hydroperoxide (LHP) and malondialdehyde (MDA), nitric oxide (NO) products, including nitrite (NO(2)(-)), nitrate (NO(3)(-)), and total nitrite (TNO(2)(-)) were found to be significantly elevated with a concomitant depletion of antioxidants in HNSCC patients as compared to tobacco users and normal controls. These derangements were also evident albeit to a lesser degree in tobacco users as compared to normal controls. Results from this study demonstrate a potential involvement of both ROS and RNS in the pathogenesis of HNSCC and also illustrate the risk of ROS/RNS induced damage healthy tobacco users are exposed to, implicating their higher risk for upper aerodigestive tract cancer.

Topics: Adult; Aged; Aged, 80 and over; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Carcinoma, Squamous Cell; Catalase; Female; Glutathione; Glutathione Peroxidase; Head and Neck Neoplasms; Humans; Lipid Peroxidation; Lipid Peroxides; Male; Malondialdehyde; Middle Aged; Nitrates; Nitric Oxide; Nitrites; Reactive Nitrogen Species; Reactive Oxygen Species; Smoking; Superoxides

Bile acids are often refluxed into the lower oesophagus and are candidate carcinogens in the development of oesophageal adenocarcinoma. We show here that the secondary bile acid, deoxycholic acid (DCA), is the only one of the commonly refluxed bile acids tested here, to show genotoxicity, in terms of chromosome damage and mutation induction in the human p53 gene. This genotoxicity was apparent at both neutral and acidic pH, whilst there was a considerable increase in bile-induced toxicity at acidic pH. The higher levels of cell death and low cell survival rates at acidic pH may imply that acid bile exposure is toxic rather than carcinogenic, as dead cells do not seed cancer development. We also show that DCA (at neutral and acid pH) induced the release of reactive oxygen species (ROS) within the cytoplasm of exposed cells. We further demonstrate that the genotoxicity of DCA is ROS mediated, as micronucleus induction was significantly reduced when cells were treated with DCA + the anti-oxidant vitamin C. In conclusion, we show that DCA, is an effective genotoxin at both neutral and acidic pH. As bile acids like DCA can induce DNA damage at neutral pH, suppressing the acidity of the refluxate will not completely remove its carcinogenic potential. The genotoxicity of DCA is however, ROS dependent, hence anti-oxidant supplementation, in addition to acid suppression may block DCA driven carcinogenesis in Barrett's patients.

Topics: Adenocarcinoma; Antioxidants; Ascorbic Acid; Barrett Esophagus; Carcinoma, Squamous Cell; Cell Survival; Deoxycholic Acid; Detergents; DNA Damage; Esophageal Neoplasms; Humans; Hydrogen-Ion Concentration; Micronucleus Tests; Reactive Oxygen Species; Tumor Cells, Cultured; Tumor Suppressor Protein p53

Oxidative stress by reactive oxygen species (ROS) and nitrosative stress by reactive nitrogen species (RNS) are proven initiators and promoters in carcinogenesis. Elevated ROS/RNS with lowered antioxidants occur in patients with squamous cell carcinoma of oral cavity. Ours is the first study to evaluate the effect of curative resection on both oxidative and nitrosative stress in such patients.. This study was conducted on 24 cancer patients and with age- and sex-matched healthy controls. Lipid peroxidation products, nitric oxide (NO) products and ceruloplasmin (CPL) in plasma were measured before and after surgery. Similarly enzymatic antioxidants in erythrocytes and non-enzymatic antioxidants in plasma were measured.. Statistically significant elevation of lipid peroxidation, NO products and CPL and depletion of antioxidants were found in cancer patients compared with controls. After curative surgical resection there was a statistically significant fall in oxidants and CPL coupled with a rise in antioxidants.. Our results suggest that oxidative/nitrosative stress could play a significant role in oral cavity cancer (OCC) and that curative resection is effective in alleviating this oxidative/nitrosative burden. Significant mitigation of oxidative/nitrosative stress could indicate the completeness of resection since tumor forms the major source of oxidants.

Topics: Adult; Ascorbic Acid; Carcinoma, Squamous Cell; Case-Control Studies; Female; Glutathione; Glutathione Transferase; Humans; Lipid Peroxidation; Lipid Peroxides; Male; Malondialdehyde; Middle Aged; Mouth Neoplasms; Nitrates; Nitric Oxide; Nitrites; Oxidative Stress; Oxidoreductases; Preoperative Care; Prospective Studies; Vitamin E

To investigate the associations between intake of antioxidant nutrients and risk of basal cell (BCC) and squamous cell carcinomas (SCC) of the skin, we carried out a prospective study among 1001 randomly selected adults living in an Australian community. Intake of antioxidants was estimated in 1996. Incident, histologically-confirmed BCC and SCC were recorded between 1996 and 2004. High dietary intake of lutein and zeaxanthin was associated with a reduced incidence of SCC in persons who had a history of skin cancer at baseline (highest versus lowest tertile, multivariable adjusted relative risk (RR)=0.47, 95% confidence interval (CI): 0.25-0.89; P for trend=0.02). In persons without a history of skin cancer at baseline, development of BCC was positively associated with intake of vitamins C and E from foods plus supplements (RR=3.1, 95% CI: 1.1-8.6; P for trend=0.03 and RR=2.6, 95% CI: 1.1-6.3; P for trend=0.02, respectively). In those with a skin cancer history at baseline, dietary intake in the second tertile for beta-carotene (multivariable adjusted RR=2.2, 95% CI: 1.2-4.1) and for vitamin E (multivariable adjusted RR=2.1, 95% CI: 1.1-3.9) was associated with increased BCC risk, with no trend, and similar results were seen in those with a specific history of BCC. These data suggest quite different associations between antioxidant intake and SCC compared with BCC, consistent with other evidence of their different causal pathways.

Topics: Aged; Antioxidants; Ascorbic Acid; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Carotenoids; Epidemiologic Methods; Female; Humans; Male; Middle Aged; Queensland; Selenium; Skin Neoplasms; Vitamin E

Our objective was to examine prospectively the intake of vitamins A (including retinol and total vitamin A), C and E; folate; total carotene; and several individual carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin and lutein/zeaxanthin) in relation to incidence of SCC of the skin in 2 large cohorts of men and women. We used a prospective cohort study design with up to 14 years of follow-up in women and 10 years in men. Diet was measured with FFQs every 2-4 years; cases of SCC of the skin were ascertained on biennial questionnaires and confirmed by medical records. Participants were female nurses and male health professionals, from the Nurses' Healthy Study and the Health Professionals Follow-up Study in the United States, without a history of any cancer in 1982 (n = 85,944 women) and 1986 (n = 43,867 men). Follow-up response was achieved for over 90% of potential person-years. Relative risks and 95% confidence intervals for development of SCC of the skin are reported. We recorded 369 cases of SCC in women and 305 cases in men. After multivariate adjustment for various known behavioral, sun-exposure and sun-sensitivity risk factors for SCC, there were no significant inverse associations between these dietary factors and SCC incidence. No evidence was found that vitamins A, C and E; folate; or carotenoids play an important protective role against incident SCC.

Topics: Adult; Aged; Ascorbic Acid; Carcinoma, Squamous Cell; Carotenoids; Cohort Studies; Female; Humans; Incidence; Male; Middle Aged; Prospective Studies; Risk Factors; Sensitivity and Specificity; Skin Neoplasms; United States; Vitamin A; Vitamin E

To investigate and analyze changes in irradiated salivary gland function of patients with head and neck tumors treated with radiotherapy.. Thirty-seven patients with head and neck tumors, who received 40-70 Gy of irradiation to all major salivary glands, were analyzed. The weights of saliva secreted for 10 minutes at rest, and for 5 minutes with vitamin C stimulation, were measured. The salivary gland function was defined by the weight of saliva.. With vitamin C stimulation, the weight of saliva in patients whose doses were < or =50 Gy, was significantly higher than that of patients whose doses were > or = 58 Gy (2.48 +/- 0.33 g vs. 0.73 +/- 0.18 g, P = 0.0003). When doses administered to salivary glands were < or =50 Gy, the stimulated saliva secretion recovered over time, after irradiation. However, when the doses of irradiation were > or = 58 Gy, there was no recovery in saliva secretion even after a few years. Multiple regression analysis showed that age and chemotherapy may not affect salivary gland function even years after radiotherapy.. When salivary glands were irradiated with doses < or =50 Gy, gradual recovery of salivary gland function was observed over time, whereas there was no significant recovery when the irradiation dose was >58 Gy.

Topics: Adolescent; Adult; Aged; Ascorbic Acid; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Radiotherapy Dosage; Saliva; Salivary Glands

To test the hypothesis that there is a link between plasma glutathione (GSH) or other antioxidants (uric acid, ascorbate) and the severity of radiation mucositis following radiation treatment of tumors of the head and neck.. Patients with carcinomas of the head-and-neck region were treated with the continuous hyperfractionated accelerated radiotherapy (CHART) regimen (54 Gy in 36 fractions over 12 days). Samples of blood plasma were analyzed for GSH, cysteine, urate, and ascorbate by high-pressure liquid chromatography. Patients were graded for dysphagia and requirement for analgesics. The areas under the curves of scores over 2-6 weeks following treatment were computed, and Spearman's rank-correlation coefficient was used to test for an association between plasma GSH levels (or those of other antioxidants) and mucositis.. The pretreatment plasma GSH level in 18 patients scored in the study was 1.0 +/- 0.7 M. Analysis of these and the dysphagia scores produced a correlation coefficient of 0.22 (confidence interval -0.28, 0.61; p = 0.39). No correlation was seen between mucositis severity and other measures of plasma antioxidants: cysteine (7.6 +/- 1.7 M), cysteine + GSH (8.6 +/- 1.9 M), uric acid (317 +/- 86 M), ascorbate (29 +/- 20 M), or whole-blood GSH concentrations (1,010 +/- 239 M).. The measurements of approximately micromolar levels of plasma GSH, or about 10 M cysteine + GSH (almost all of the total nonprotein thiols), are consistent with most other published data for either healthy adults or cancer patients; however, the values reported in an earlier study, suggesting a link between GSH and mucositis, are much higher. The hypothesis of a possible link between radiation mucositis and plasma-free (nonprotein) thiols was not supported.

Topics: Ascorbic Acid; Carcinoma, Squamous Cell; Cysteine; Dose Fractionation, Radiation; Glutathione; Humans; Linear Models; Mouth Mucosa; Mouth Neoplasms; Sensitivity and Specificity; Stomatitis; Uric Acid

Cigarette smokers are known to have lower concentrations of circulating ascorbic acid than nonsmokers. In contrast, there is evidence that the extracellular fluid lining of the alveolus, which comes in close contact with cigarette smoke, and the alveolar macrophages of smokers are enriched with ascorbic acid. The clinical significance of these observations is unknown.. The authors measured the ascorbic acid concentrations and radiolabeled methyl incorporation (which is inversely related to the degree of DNA methylation in vivo) of paired samples of squamous cell carcinoma (SCC) and adjacent uninvolved mucosa of the lung and larynx (n = 22).. Cancerous tissues had significantly higher ascorbic acid concentrations (mean +/- standard deviation [SD, 485 +/- 77; median, 483 ng/mg protein) compared with their matched uninvolved tissues (mean +/- SD, 151 +/- 52; median, 72 ng/mg protein; P < 0.0001). The radiolabeled methyl incorporation was significantly higher in cancerous tissues (mean +/- SD, 31,419 +/- 2629; median, 31,416 counts per minute [CPM]/microg DNA) compared with their matched uninvolved tissues (mean +/- SD, 11,883 +/- 1567; median, 11,444 CPM/microg DNA; P < 0.0001). The Spearman correlation between ascorbic acid concentrations and radiolabeled methyl incorporation by DNA in SCCs was inverse and statistically significant (r = -0.58, P = 0.008), indicating a beneficial effect of accumulated ascorbic acid in global methylation of DNA. In the uninvolved tissues, this correlation was inverse but statistically not significant (r = -0.20, P =0.35).. Cancerous tissues of the lung and larynx demonstrated their ability to accumulate ascorbic acid. The accumulation of ascorbic acid by these tissues seemed to facilitate global methylation of DNA.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Carcinoma, Squamous Cell; DNA Methylation; Female; Humans; Laryngeal Neoplasms; Lung Neoplasms; Male; Middle Aged; Smoking

To evaluate the role of vitamins C and E as chemopreventive agents in oral carcinogenesis by optical and ultrastructural studies.. The cheek pouch of male hamsters was treated with the oral carcinogen, dimethylbenz(a)anthracene (DMBA), to induce multiple tumour formation. Vitamins C and E were applied either singly or in combination as a chemopreventive agent. Paraffin and resin-embedded sections of the hamster cheek pouch were studied optically and ultrastructurally.. The epithelium of control hamsters showed hyperorthokeratosis and parakeratosis, but did not develop well differentiated squamous cell carcinoma (WDSCC). Ninety percent of the animals treated with DMBA alone showed WDSCC while 10% of the animals developed papillomas. There was also a marked increase in the number of cells undergoing mitosis in this group. A reduction in the yield (1.1 tumour/animal) and rate 60-80% of squamous cell carcinomas but not of papillomas (2.0 papillomas/animal) was observed in groups VI-VIII treated with DMBA and vitamins C and E singly or in combination as compared to those of DMBA only. In animals treated with DMBA plus vitamins C and E, statistical significant decrease in the number of animals with tumours and mitotic basal cells was observed when compared with the DMBA treated group. Control animals showed normal ultrastructural morphology while tumour-bearing animals showed basal lamina in a discontinuous, fragmented, broken and diffused basement membrane, with diminished lamina densa, fewer hemidesmosomes and invagination of the basal cell cytoplasmic processes in the subepithelium.. These results indicate that vitamin E singly or in combination with vitamin C plays a role in the inhibition of tumour cell growth.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; Basement Membrane; Carcinogens; Carcinoma, Squamous Cell; Cheek; Chemoprevention; Chi-Square Distribution; Cricetinae; Cytoplasm; Drug Combinations; Epithelium; Hemidesmosomes; Leukoplakia, Oral; Male; Mesocricetus; Mitosis; Mouth Mucosa; Mouth Neoplasms; Papilloma; Parakeratosis; Vitamin E

Antioxidant vitamins have attracted considerable attention in previous studies of esophageal squamous-cell carcinoma, but dietary studies of adenocarcinoma of the esophagus and gastric cardia remain sparse. Treating these tumors as distinct diseases, we studied intakes of vitamin C, beta-carotene and alpha-tocopherol in a nationwide population-based case-control study in Sweden, with 185, 165, and 258 cases of esophageal adenocarcinoma, esophageal squamous-cell carcinoma, and gastric cardia adenocarcinoma, respectively, and 815 controls. Subjects with a high parallel intake of vitamin C, beta-carotene, and alpha-tocopherol showed a 40-50% decreased risk of both histological types of esophageal cancer compared with subjects with a low parallel intake. Antioxidant intake was not associated with the risk of gastric cardia adenocarcinoma. Separately, vitamin C and beta-carotene reduced the risk of esophageal cancers more than alpha-tocopherol. We found that antioxidant intake is associated with similar risk reductions for both main histological types of esophageal cancer. Our findings indicate that antioxidants do not explain the diverging incidence rates of the 2 histological types of esophageal cancer. Moreover, our data suggest that inverse associations with esophageal squamous-cell carcinoma and adenocarcinoma may be stronger among subjects under presumed higher oxidative stress due to smoking or gastroesophageal reflux, respectively. Our results may be relevant for the implementation of focused, cost-effective preventive measures.

Topics: Adenocarcinoma; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Carcinoma, Squamous Cell; Cardia; Case-Control Studies; Diet; Dietary Supplements; Drug Synergism; Esophageal Neoplasms; Female; Gastroesophageal Reflux; Humans; Male; Multivariate Analysis; Oxidative Stress; Risk Factors; Smoking; Stomach Neoplasms; Sweden; Vitamin E

The inhibitory effects of N-(4-hydroxyphenyl)retinamide (4HPR) on the process of carcinogenesis are not fully understood and may result from its ability to induce apoptosis in transformed cells. This study investigated the apoptotic properties of 4HPR in four human cutaneous squamous cell carcinoma cell lines. Apoptosis induction, detected by the terminal deoxynucleotidyl transferase dUTP nick end labeling method, occurred in a dose- and time-dependent fashion after treatment with 4HPR. 4HPR promoted reactive oxygen species (ROS) determined by oxidation of 2',7'-dichlorofluorescin. 4HPR-induced ROS, and apoptosis could be inhibited by L-ascorbic acid. Rhodamine 123 retention revealed that 4HPR treatment promoted a gradual dissipation of mitochondrial inner transmembrane potential, and this could be inhibited by L-ascorbic acid, implying that mitochondrial permeability transition was involved in apoptosis induction. Cyclosporin A and bongkrekic acid inhibited dissipation of mitochondrial inner transmembrane potential, ROS production, and DNA fragmentation after exposure to 4HPR, demonstrating that mitochondrial permeability transition was a central coordinating feature of 4HPR-induced apoptosis.

Topics: Anticarcinogenic Agents; Apoptosis; Ascorbic Acid; Carcinoma, Squamous Cell; Cell Division; Cyclosporine; DNA Fragmentation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Enzyme Inhibitors; Fenretinide; Fluoresceins; Fluorescent Dyes; Humans; Intracellular Membranes; Membrane Potentials; Mitochondria; Oxidation-Reduction; Permeability; Reactive Oxygen Species; Rhodamine 123; Skin Neoplasms; Tumor Cells, Cultured

The combination of hydroxocobalamin (vitamin B12b) and ascorbic acid (vitamin C) can cause the death of tumor cells at the concentrations of the components at which they are nontoxic when administered separately. This cytotoxic action on epidermoid human larynx carcinoma cells HEp-2 in vitro is shown to be due to the hydrogen peroxide generated by the combination of vitamins B12b and C. The drop in the glutathione level preceding cell death was found to be the result of combined action of the vitamins. It is supposed that the induction of cell death by combined action of vitamins B12b and C is connected to the damage of the cell redox system.

Topics: Ascorbic Acid; Carcinoma, Squamous Cell; Cell Division; Drug Synergism; Glutathione; Humans; Hydrogen Peroxide; Laryngeal Neoplasms; Oxidation-Reduction; Tumor Cells, Cultured; Vitamin B 12

The induction of apoptosis by the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4HPR) has been documented in vitro in various cancer types. A role for reactive oxygen species (ROS) in apoptosis induced by 4HPR in some cancer cells has been demonstrated recently. We studied five different human head and neck and five lung cancer cell lines to determine whether the ROS play a general role in 4HPR-induced apoptosis. We found that 4HPR induced apoptosis in all of the cell lines; however, this effect was blocked by antioxidants in only 2 of the 10 cell lines. 4HPR induced a greater than 4-fold increase in the generation of intracellular ROS in these two cell lines compared with a much lower effect in other cell lines. Furthermore, these two cell lines were most sensitive to the induction of apoptosis by 4HPR. The level of the cellular antioxidant thiol and superoxide dismutase activity were relatively lower in cells, which responded to 4HPR with a high level of ROS generation. These results indicate that although ROS can mediate 4HPR-induced apoptosis in some cells, which may have a low endogenous cellular antioxidant levels, other mechanisms exist for 4HPR-induced apoptosis. One such mechanism may involve retinoic acid receptors (RARs) because an RAR antagonist was able to block partially 4HPR-induced apoptosis. In conclusion, 4HPR-induced apoptosis involves at least three different mechanisms, which are complex and can overlap in the same cell line: (a) one mechanism involving 4HPR-induced ROS; (b) one involving RARs; and (c) at least one that does not involve ROS or RARs and remains unclear.

Topics: Antineoplastic Agents; Antioxidants; Apoptosis; Ascorbic Acid; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Fenretinide; Head and Neck Neoplasms; Humans; Lung Neoplasms; Naphthalenes; Neoplasm Proteins; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Receptors, Retinoic Acid; Sulfhydryl Compounds; Superoxide Dismutase; Tumor Cells, Cultured

Reactive oxygen species (ROS), represented by superoxide, hydrogen peroxide and hydroxyl radicals, have been implicated in many diseases including cancer. ROS have been known to play an important role in the initiation and promotion of multistep carcinogenesis. The cellular antioxidants play a crucial role in protection against neoplastic disease. However, very little is known about the antioxidant defense in cervical carcinoma. This is addressed in the present study. Lipid peroxides, glutathione content and the activities of antioxidant enzymes, together with vitamin C and E content, were estimated in patients who had carcinoma of the cervix, and the values were compared with those of normal women. The results showed a remarkable reduction in the content of glutathione, vitamin E and C. Activities of glutathione peroxidase and superoxide dismutase were also reduced in cervical cancer compared to normal controls (P < 0.001). This reduction was more marked in late stages (III, IV) than in early stages (I, II) (P < 0.001). Glutathione was reduced more in poorly differentiated tumors (grade III) than in well and moderately differentiated ones (grade I, II) (P < 0.05). Levels of lipid peroxides were found to be significantly higher in malignant than in normal tissue samples and their levels were correlated with advanced clinical stage (P < 0.001). Our results suggest impaired antioxidant status in carcinoma of the cervix. This impairment is related to tumor progression.

Topics: Adenocarcinoma; Antioxidants; Ascorbic Acid; Carcinoma, Squamous Cell; Female; Glutathione; Glutathione Peroxidase; Humans; Lipid Peroxidation; Lipid Peroxides; Superoxide Dismutase; Uterine Cervical Neoplasms; Vitamin E

An increasing number of reports suggest that diet has an impact on oesophageal cancer risk in Western countries, where alcohol and tobacco are held to be the major determinants of the risk. The aim of our study was to identify dietary factors influencing the risk of oesophageal cancer in France and to determine whether certain of these could explain some of the geographical variations. We conducted a multicentre case-control study in 3 regions expected to have different diet and drinking habits (Normandy, Burgundy and Midi Pyrénées). Two hundred eight cases and 399 controls, all males, were interviewed about their eating, drinking and smoking habits. After proper adjustment for drinking and smoking, high consumption of butter and low consumption of fresh fish, vegetables and fruits were associated strongly and independently with an increase in oesophageal-cancer risk. Consistently, cholesterol appeared as a risk factor and vitamin E, vitamin D and phosphorus as independent protective factors. The protective effect of citrus and other fresh fruits (vitamin C) was confined strictly to heavy drinkers. Our findings suggest that more than one-third of the high incidence of oesophageal cancer in northwest France could be explained by the local excess in butter consumption, whereas geographical variations in consumption of dietary protective factors could explain no more than 10% of it. Overall, a large proportion (57%) of the excess incidence of oesophageal cancer in northwest France could be explained by local dietary habits, e.g., drinking hot Calvados liquor and excessive consumption of butter.

Topics: Alcohol Drinking; Animals; Ascorbic Acid; Butter; Carcinoma, Squamous Cell; Case-Control Studies; Diet; Dietary Fats; Esophageal Neoplasms; France; Fruit; Humans; Male; Multicenter Studies as Topic; Seafood; Smoking; Vegetables; Vitamin D; Vitamin E

Environmental exposure to ultraviolet light B (UVB, wave lengths 290-320 nm) of the solar spectrum causes major damage, including an inflammatory response, in skin. In the present study, we estimated the ability of a stable derivative of ascorbic acid, ascorbic acid 2-O-alpha-glucoside (AA-2G), to reduce UVB damage, using the human keratinocyte cell line, SCC, established from squamous cell carcinoma. By pre- (9 h) and post-cultivation with AA-2G, a significant preventive effect on the decrease in the absolute number of surviving cells by exposure to UVB (typical dose, 20 mJ/cm2) was measurable by a neutral red-uptake assay. The release of lactate dehydrogenase from the cell membrane damaged by UVB was inhibited by AA-2G. In agarose gel electrophoresis, relatively high molecular weight DNA fragments were detected in irradiated cells after 6 h post-irradiation, suggesting that the mechanism of cell death was necrosis. Quantitative analysis of DNA content by flow cytometry indicated that AA-2G suppressed both an increase in debris with degraded nuclei and a decrease in cells in G1 and S phases, but not in the G2/M phase, by UVB exposure. These data suggest that AA-2G shows a photoprotective effect against UVB-induced damage in human epithelial cells.

Topics: Ascorbic Acid; Carcinoma, Squamous Cell; Cell Death; DNA; Flow Cytometry; Humans; Keratinocytes; L-Lactate Dehydrogenase; Radiation-Protective Agents; Skin Neoplasms; Tumor Cells, Cultured; Ultraviolet Rays

We have reported that ascorbate radical (Asc.-) could serve as an indicator of the amount of hydroxyl radical and superoxide produced by irradiation in vivo. Using this method, we investigated the relationship between tumor size and Asc.- production after irradiation (10 Gy) and between tumor size and the radical-scavenging ability of WR-2721 (300 mg/kg). Asc.- was measured in normal muscle and SCC-VII tumors transplanted into mice (n = 6). In tumors, the increase in Asc.- significantly decreased with increasing tumor size (r = -0.483; P < 0.05). The increase in Asc.- production after irradiation was more inhibited by WR-2721 in normal muscle tissue than in tumor tissue at various sizes. In tumors, the increase in Asc.- was less inhibited by WR-2721 with increasing tumor size. These results demonstrate that the increase in radical production after irradiation and drug distribution decreased with increasing tumor size and that WR-2721 has excellent differential protection. This method is expected to measure changes in the amounts of local hydroxyl radical and superoxide modified by a change of tumor environment or drug administration.

Topics: Amifostine; Animals; Ascorbic Acid; Carcinoma, Squamous Cell; Male; Mice; Mice, Inbred C3H; Muscle, Skeletal; Radiation-Protective Agents

We measured ascorbate radical (AR) produced by the reaction of ascorbic acid (Asc) with hydroxyl radical (.OH) or superoxide (O2-) after irradiation in normal muscle and SCC-VII tumor of C3H/He mice. AR can be measured using electron spin resonance (ESR) equipment and the dialysis method. The tube for collecting AR was inserted such that the dialysis membrane was in contact with the normal thigh or the center of the tumor lesion. The AR in the interstitial fluid around the membrane was collected through the dialysis membrane. After irradiation with 10 Gy, AR increased in both the normal muscle and tumor tissue; the percent increase was 53.1% for normal muscle tissue and 33.8% for tumor tissue. The maximum percent increases in AR in the normal muscle and the tumor tissue were 11.7 and 9.5% for 2.5 Gy, 28.5 and 18.5% for 5 Gy, 53.1 and 33.8% for 10 Gy, and 88.5 and 44.8% for 15 Gy, respectively. The amount of AR increased to maximums of 144.3% and 160.1% after treatment with H2O2 and FeCl2, respectively, while it decreased to minimums of 65.3% and 81.3% after treatment with superoxide dismutase (SOD) and catalase, respectively. These results suggest that the amount of .OH and O2- is reflected in the amount of AR production. This method is useful for the following reasons. First, no special treatment, such as freezing of the samples, and no administration of noxious agents are necessary. Second, irradiation using a dose of only several Gy shows an increase in the production of AR. Third, this method is less invasive.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Ascorbic Acid; Carcinoma, Squamous Cell; Dose-Response Relationship, Radiation; Electron Spin Resonance Spectroscopy; Free Radicals; Hydroxides; Male; Mice; Mice, Inbred C3H; Radiation Dosage; Superoxides

In experiments involving the induction of squamous cell carcinoma in 1846 hairless mice that were maintained on a wide variety of diets, it was found that those diets with the least optimum balance of nutrients had the greatest inhibitory effect on growth of cancer. Rate of onset and severity of tumors was caused to vary over a 20-fold range by means of dietary balance alone. These experiments suggest that dietary variation in general and intentional malnutrition in particular should be given special attention in the control of existing cancer in humans.

Topics: Animal Feed; Animals; Ascorbic Acid; Carcinoma, Squamous Cell; Diet; Dietary Proteins; Female; Fruit; Mice; Mice, Hairless; Neoplasms, Radiation-Induced; Nutrition Disorders; Skin Neoplasms; Ultraviolet Rays; Vegetables; Vitamin E

In experiment I, short-term effects of combined treatment with anti-oxidants, sodium ascorbate (NaAsA) and sodium nitrite (NaNO2) on forestomach cell proliferation were examined in F344 male rats. Groups of 5 animals aged 6 weeks were treated for 4 weeks with 0.8% catechol, 0.8% hydroquinone, 1% tert-butyl-hydroquinone (TBHQ), 2% gallic acid or 2% pyrogallor alone or in combination with 0.3% NaNO2 in the drinking water and/or 1% NaAsA in the diet. The thicknesses of forestomach mucosa in rats treated with anti-oxidants and NaNO2 in combination were greater than those with antioxidant alone and additional NaAsA treatment further enhanced the thickening of mucosa. It was noteworthy that values for mucosae of animals treated with NaNO2 and NaAsA without anti-oxidant were similar to those for anti-oxidants. In experiment 2, effects of combined treatment with NaAsA or ascorbic acid (AsA) and NaNO2 on carcinogenesis were examined in F344 male rats with or without N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) pre-treatment. Groups of 20 or 15 rats, respectively, aged 6 weeks, were given a single intra-gastric administration of 150 mg/kg body weight of MNNG in DMSO:water = 1:1 or the vehicle alone by stomach tube. Starting 1 week later, they received supplements of 1% NaAsA or 1% AsA in the diet and 0.3% NaNO2 in drinking water in combination, each of the individual chemicals alone, or basal diet until the end of week 52. In MNNG-treated animals, incidences of forestomach papillomas and carcinomas were significantly enhanced in the NaNO2 alone group (84 and 47%, respectively) as compared with the basal diet group (30 and 10%), with further significant increase in carcinomas occurring with additional NaAsA (79%, p < 0.05) or AsA (85%, p < 0.05) treatment. In animals without MNNG, all animals in the NaNO2 group demonstrated mild hyperplasia, additional administration of NaAsA or AsA remarkably enhancing the grade of hyperplasia, and resulting in 53% and 20% incidences, respectively, of papillomas. Thus NaNO2 was demonstrated to exert promoter action for forestomach carcinogenesis, with NaAsA and AsA acting as co-promoters. The results strongly indicate that combined treatment with NaAsA or AsA and NaNO2 may induce forestomach carcinomas in the long term.

Topics: Animals; Ascorbic Acid; Body Weight; Carcinoma, Squamous Cell; Drug Interactions; Kidney; Liver; Male; Methylnitronitrosoguanidine; Organ Size; Papilloma; Rats; Rats, Inbred F344; Sodium Nitrite; Stomach Neoplasms

Forty young adult male Syrian hamsters (Mesocricetus auratus) were divided into four groups of 10 animals. The animals in group 1 (tumor control) had the right buccal pouches painted three times a week with a 0.5% solution of 7,12 dimethylbenz(a)anthracene in heavy mineral oil USP with the use of a number 4 sable brush. The animals in group 2 (experimental group) had the right buccal pouches painted with the same solution as group 1. In addition, they received 1 mg ascorbic acid in 0.5 ml mineral oil three times a week on days alternating with the other application. The ascorbic acid was administered by mouth with the use of a pipette. The animals in group 3 received 1 mg ascorbic acid in 0.5 ml mineral oil three times weekly, and the animals in group 4 were untreated controls. The animals were killed after 14 weeks. Tumors were counted and measured. Both right and left (control) pouches were photographed, excised, fixed in formalin, sectioned in paraffin, and studied histologically. The animals that received the ascorbic acid (vitamin C) had significantly larger tumors in the right buccal pouch, although actual numbers of gross tumors were only slightly increased. The figures for tumor burden in the animals in groups 1 and 2 were 364 versus 648 mm3. Histologic study revealed that the animals in group 2 had more anaplastic tumors and a significantly greater number of areas of dysplastic leukoplakia than the animals in group 1.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Ascorbic Acid; Carcinogens; Carcinoma, Squamous Cell; Cheek; Cocarcinogenesis; Cricetinae; Drug Synergism; Leukoplakia, Oral; Male; Mesocricetus; Mouth Neoplasms

Selenium has been suggested to be anticarcinogenic and to play a role in the cellular defense against oxidative stress. The association between toenail selenium (a marker of long-term selenium status) and lung cancer was investigated in a cohort study of diet and cancer that started in 1986 among 120,852 Dutch men and women aged 55-69 years. After 3.3 years of follow-up, 550 incident cases of lung carcinoma were detected. Toenail selenium data were available for 370 lung cancer cases and 2459 members of a randomly selected subcohort. The rate ratio of lung cancer for subjects in the highest compared to the lowest quintile of toenail selenium, after controlling for age, gender, smoking, and education, was 0.50 (95% confidence interval, 0.30-0.81), with a significant inverse trend across quintiles (P = 0.006). The protective effect of selenium was concentrated in subjects with a relatively low dietary intake of beta-carotene or vitamin C. The rate ratio in the highest compared to the lowest quintile of selenium was 0.45 in the low beta-carotene group (95% confidence interval, 0.22-0.92; trend P = 0.028) and 0.36 in the low vitamin C group (95% confidence interval, 0.17-0.75; trend P < 0.001). The results of this study support an inverse association between selenium status and lung cancer and suggest a modification of the effect of selenium by the antioxidants beta-carotene and vitamin C.

Topics: Adenocarcinoma; Age Factors; Aged; Ascorbic Acid; beta Carotene; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Carotenoids; Cohort Studies; Education; Feeding Behavior; Female; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Nails; Netherlands; Prospective Studies; Risk Factors; Selenium; Sex Factors; Smoking; Surveys and Questionnaires; Time Factors; Toes; Vitamin A

We examined the effects of flavone and two polyhydroxylated plant flavonoids (quercetin and fisetin), either singly or in combination with ascorbic acid, on the growth of a human squamous cell carcinoma cell line (HTB 43) in vitro. Fisetin and quercetin significantly impaired cell growth in the presence of ascorbic acid. Exposure of cells to ascorbic acid (2 micrograms/ml) and 2 micrograms/ml of either fisetin or quercetin resulted in 61 and 45% inhibition of cell growth, respectively, in 72 h, while treatment with ascorbic acid alone had no effect on cellular proliferation. Flavone and ascorbic acid, either as single agents or in combination, exhibited no significant inhibition at any of the concentrations tested. The enhancement of the antiproliferative effect of the above flavonoids by ascorbic acid may be due to its ability to protect these compounds against oxidative degradation.

Topics: Adjuvants, Pharmaceutic; Antineoplastic Agents, Phytogenic; Ascorbic Acid; Carcinoma, Squamous Cell; Cell Division; Cell Line; Drug Synergism; Flavonoids; Humans; Tumor Cells, Cultured

Six synthetic 2,6-dimethoxyhydroquinone derivatives were shown to have different degrees of cytotoxicity to two human tumor cell lines (KB and PC-9) under the synergistic activation of L-ascorbic acid. Two representative compounds displayed very low time-schedule-independent index, showing that the cytotoxic action is independent of time of drug treatment. The addition of catalase produced a significant inhibitory effect on the cytotoxicity of two representative compounds, indicating that the cytotoxic action is mediated by the generation of H2O2, which may yield hydroxyl radicals via various mechanisms. ESR studies employing the spin-trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) showed that massive hydroxyl radicals were generated from four of these drugs as a non-linear function of L-ascorbic acid concentration. The results indicate the possible involvement of hydroxyl radicals in the cytotoxic action of these novel drugs.

Topics: Adenocarcinoma; Aminacrine; Antineoplastic Agents; Ascorbic Acid; Carcinoma, Squamous Cell; Catalase; Drug Interactions; Electron Spin Resonance Spectroscopy; Humans; Hydroquinones; Hydroxides; Hydroxyl Radical; Lung Neoplasms; Mouth Neoplasms; Time Factors; Tumor Cells, Cultured

Dietary levels of vitamins C and E have been associated with cancer prevention and to a lesser extent with therapeutic enhancement of cancer treatment. Inhibition of prostaglandins (PGs) by pharmacological agents has been demonstrated to enhance immunocompetence, and to suppress growth of tumors in animals and humans. We report here on the effect of vitamins C and E on PGE2 production by human gingival fibroblasts and SCC-25 oral squamous carcinoma cells. The results indicate: 1. vitamins C and E exert a dose-dependent effect on arachidonic acid (AA) release and PGE2 synthesis; 2. vitamin E has a biphasic effect which is stimulatory at 1 and 10 microM and inhibitory at 100 microM; 3. vitamin E is considerably more potent than vitamin C in its inhibitory effect on AA and PGE2 in both cell types; 4. a combination of the two vitamins has a consistent dose-dependent inhibitory effect on AA and PGE2; 5. vitamin C stimulates PGE2 synthesis from exogenous AA in fibroblasts, and inhibits it in SCC-25 cells. The in vivo significance of these findings requires further investigation.

Topics: Adult; Arachidonic Acid; Ascorbic Acid; Carcinoma, Squamous Cell; Cell Line; Dinoprostone; Female; Fibroblasts; Gingiva; Humans; Tongue Neoplasms; Tumor Cells, Cultured; Vitamin E

Radioactivity measurements and autoradiographic studies of DNA, RNA and protein synthesis using [3H]-thymidine, [3H]-uridine and [3H]-leucine revealed that Vitamin C administration significantly (by 50%) decreases the DNA, RNA and protein synthesis in the neoplastic cells of basal cell carcinomas and squamous cell carcinomas in mice and rats. Basal cell carcinomas and squamous cell carcinomas were induced by a topical application of a chemical carcinogen, 3-methylcholanthrene. The inhibition of DNA, RNA and protein synthesis is accompanied by advanced ultrastructural and cell surface changes. Since the concentrations of Vitamin C were significantly higher in the plasma of Vitamin C-treated as compared to that of non Vitamin C-treated animals, these findings demonstrate that Vitamin C inhibits DNA, RNA and protein synthesis in neoplastic epithelial cells, and thus exerts its antineoplastic effect.

Topics: Animals; Ascorbic Acid; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; DNA; Epithelium; Male; Methylcholanthrene; Mice; Protein Synthesis Inhibitors; Rats; Rats, Inbred Strains; RNA

A study of 748 cases and 1,411 hospital and community controls in four Latin American countries evaluated the association between certain elements of diet and invasive cervical cancer. Subjects were interviewed about their adult consumption of 58 food items, including the major sources of putative protective agents (vitamin A, carotenoids, vitamin C, and folacin) as well as other behavioral and medical characteristics related to cervical cancer. Participation rates were above 95% for both cases and controls. After adjustment for age, study site, sexual and reproductive behavior, socioeconomic status, screening practices, and detection of human papillomavirus 16/18 by filter in situ hybridization, a slightly lower risk was observed for the highest quartiles of consumption of fruit and fruit juices, while no reductions in risk were associated with vegetables, foods of animal origin, complex carbohydrates, legumes, or folacin-rich foods. When nutrient indices were derived, significant trends of decreasing risk were observed for vitamin C (adjusted odds ratio (OR) = 0.69 for the highest vs. the lowest quartile; p for trend = 0.003), beta-carotene (OR = 0.68; p = 0.02), and other carotenoids (OR = 0.61; p = 0.003). Inclusion of vitamin C and beta-carotene in the same model attenuated the association with beta-carotene, while the association with vitamin C remained unchanged. The results are consistent with those of other investigations and provide support for a protective effect of vitamin C, carotenoids, and other substances found in the same fruits and vegetables against the development of invasive cervical cancer. However, the fact that the associations were driven by relation in two of the study sites and among women of higher socioeconomic status leaves open the possibility of selection bias or effects of unidentified aspects of dietary patterns.

Topics: Ascorbic Acid; Carcinoma, Squamous Cell; Case-Control Studies; Diet; Female; Folic Acid; Humans; Latin America; Neoplasm Invasiveness; Nutritional Status; Risk Factors; Uterine Cervical Neoplasms; Vitamin A

Vitamin C is an essential nutrient whose protective influence in carcinogenesis has been reported frequently. In general, evidence suggests that vitamin C inhibits the formation of some carcinogens and decreases the incidence and delays the onset of neoplastic lesions but the mechanisms by which this occurs are not known. In 1973, Wallenius and Lekholm induced intra-oral palatal squamous cell carcinomas by the use of the water soluble carcinogen 4-nitroquinoline-1-oxide (4NQO) applied thrice weekly to the palatal mucosa of rats. The aim of this study was to determine if in rats topically applied vitamin C had an effect on the process of carcinogenesis caused by the application of 4NQO. The results of this study showed that in the 4NQO treated animals a progression through mild, moderate and severe dysplasia occurred prior to neoplastic changes at 24 weeks and that this progression was delayed in the animals treated topically with vitamin C. It can be concluded that topically applied vitamin C has a modulating effect on the neoplastic process induced by 4NQO in the palatal mucosa of rats.

Topics: 4-Nitroquinoline-1-oxide; Administration, Topical; Animals; Ascorbic Acid; Carcinoma, Squamous Cell; Epithelium; Hyperplasia; Leukoplakia, Oral; Male; Mouth Mucosa; Mouth Neoplasms; Palate; Rats; Rats, Inbred Strains; Time Factors

The effects of sodium ascorbate (vitamin C) and 2-methyl-1,4-naphthoquinone (vitamin K3) administered separately or in combination on the in vitro cultured human neoplastic cell lines MCF-7 (breast carcinoma), KB (oral epidermoid carcinoma), and AN3-CA (endometrial adenocarcinoma) have been examined. When given separately, vitamin C or K3 had a growth inhibiting action only at high concentrations (5.10(3) mumol/1 and 10(5) nmol/l, respectively). Combined administration of both vitamins demonstrated a synergistic inhibition of cell growth at 10 to 50 times lower concentrations. At this level separately given vitamins are not toxic. The sensitivity to this treatment was somewhat different in the three cell lines, being slightly higher for KB line. This tumor cell growth inhibitory effect was completely suppressed by the addition of catalase to the culture medium containing vitamins C and K3, suggesting an excessive production of hydrogen peroxide as being implied in mechanisms responsible for the above-mentioned effects.

Topics: Adenocarcinoma; Ascorbic Acid; Breast Neoplasms; Carcinoma, Squamous Cell; Catalase; Cell Division; Drug Synergism; Female; Humans; Mouth Neoplasms; Tumor Cells, Cultured; Uterine Neoplasms; Vitamin K

Induction by interferon-gamma of indoleamine 2,3-dioxygenase (a tryptophan degradation enzyme) was examined with 11 human cell lines. The enzyme induction was demonstrated in 7 of the 11 cell lines. The induced enzyme in each of the 7 cell lines was identical to the enzyme purified from human placenta, as evidenced by immunoblot analysis with a monoclonal antibody specific to the placental one. The extent of the induction varied largely with the cell line; a relatively high induction was observed with HEL (lung fibroblasts), NY (osteosarcoma), and A-431 (epidermoid carcinoma). The enzyme induction was dependent on the concentration of interferon-gamma and occurred 12-18 h after addition of interferon-gamma to the cultures. Interferon-alpha or -beta was completely ineffective in this induction. Interferon-gamma inhibited the growth of the 7 cell lines observed with the enzyme induction, and this growth inhibition was accompanied with a complete deletion of tryptophan (less than 1 microM) in the culture medium by the induction of the enzyme. For two of these cell lines, the inhibition was partially reversed by an addition of exogenous tryptophan to the medium not to be depleted. These findings indicated that the growth inhibition by interferon-gamma was in part explained by the tryptophan depletion in the medium caused by the enzyme induction.

Topics: Ascorbic Acid; Carcinoma, Squamous Cell; Enzyme Induction; Humans; Immunosorbent Techniques; Interferon-gamma; Lung; Methylene Blue; Osteosarcoma; Oxygenases; Recombinant Proteins; Tryptophan; Tryptophan Oxygenase; Tumor Cells, Cultured

A case-control study was conducted based on 427 white males with lung cancer of the squamous, small cell, and adenocarcinoma histologic subtypes and 1,094 white male controls admitted to Roswell Park Memorial Institute between the years 1957 and 1965. The relation between selected dietary factors and lung cancer risk was examined for each histologic subtype while controlling for past cigarette use. Dietary vitamin A was found to be negatively associated with risk for squamous cell and small cell carcinoma, but not for adenocarcinoma of the lung. No significant association was observed, however, between dietary vitamin C, fats, or fiber and any of the lung cancer subtypes. These results suggest that the apparent protective effect of vitamin A in lung cancer may be histologic type-specific.

Topics: Adenocarcinoma; Adult; Aged; Alcohol Drinking; Ascorbic Acid; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Diet; Dietary Fats; Dietary Fiber; Humans; Lung Neoplasms; Male; Middle Aged; Risk; Smoking; Vitamin A

A squamous cell carcinoma (ASB XIII) and a large cell carcinoma (ASB XIV) induced from mouse lung cells by chrysotile asbestos were established in serial transplant in BALB/c mice. New hosts were treated with retinoids by ip injection at 10 mg/kg 5 days/week. Growth inhibition of ASB XIII was 58%-64% (P less than 0.005) after treatments with all-trans retinoic acid, 52% after trimethylmethoxyphenyl analog, ethyl ester, 26% (not significant) after 13-cis retinoic acid. Growth inhibition of ASB XIV was 39% (P less than 0.02) after injections of all-trans retinoic acid, and 33% (P greater than 0.05) after trimethylmethoxyphenyl analog, ethyl ester. After daily oral administration of 10 mg/kg of all-trans retinoic acid in feed, there was 61%-81% inhibition (P less than 0.005) of ASB XIII. Growth of ASB XIII was not significantly inhibited by daily im injections of 200 mg/kg of vitamin C.

Topics: Animals; Ascorbic Acid; Body Weight; Carcinoma; Carcinoma, Squamous Cell; Diet; Female; Injections, Intraperitoneal; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Probability; Retinoids

Topics: Adenocarcinoma; Animals; Antioxidants; Ascorbic Acid; Carcinoma, Squamous Cell; Male; Methylnitronitrosoguanidine; Neoplasms; Rats; Rats, Inbred F344; Sarcoma; Stomach Neoplasms

Hyperoxia induced cellular damage was used as an experimental model system for examining the ameliorative role of antioxidants. Multiplication of HEp-2 cells in monolayer culture was inhibited after exposure to 100% O2 either hyperbarically at 3 atm absolute (atma) or normobarically at 1 atma for periods from 15 s to 4 h. The inhibition was characterized by a slower rate of replication for a period from 1 to 3 d after exposure than in unexposed cultures, and then massive cellular death. Less killing followed exposure to normobaric O2 than to hyperbaric O2, and the shorter the period of exposure to hyperoxia the less killing. Addition of 100 micrograms/ml of sodium L-ascorbate to unexposed cultures enhanced growth (cell number at 6 d) almost twofold. When added ascorbate was present only during hyperoxic exposure (but not afterward), subsequent growth in air was enhanced 1.6-fold. However, when cells were exposed without added ascorbate, there was from 2 to 12-fold greater growth in air in the presence of the added ascorbate (as compared to exposed controls). This greater growth was always only a partial reversal of the lethal effect resulting from hyperoxia. Addition of 25 micrograms/ml catalase did not affect control or exposed cultures. Addition of ascorbate plus catalase was not as effective as ascorbate alone in promoting growth; the catalase moiety antagonized some of the growth enhancing influence of ascorbate. This suggests that extracellular H2O2 was not a factor in the lethal effect resulting from hyperoxia.

Topics: Ascorbic Acid; Carcinoma, Squamous Cell; Catalase; Cell Division; Cell Line; Cell Survival; Humans; Hyperbaric Oxygenation; Kinetics; Larynx

We have carried out a study of large malignant skin tumours (squamous-cell carcinomas) and other lesions in "hairless" mice (in groups of 45 or 60 mice) intermittently exposed to ultraviolet light over a period of 15 weeks, beginning when the mice were about 8 weeks old. Various groups were given a standard diet (Wayne Lab-Blox) or the same food with added vitamin C or vitamin E throughout the study. Lesions, classified by histopathologic study as atypical squamous-cell proliferations varying from early actinic keratoses to invasive poorly differentiated squamous-cell carcinomas, had begun to develop by the end of the period of irradiation. They were counted twice a month for five months. The observed fraction of mice that developed lesions during successive time periods was analyzed by the statistical method recommended by a committee of the International Agency for Research on Cancer. A pronounced effect of vitamin C in decreasing the incidence of the malignant lesions was observed with very high statistical significance. No significant effect of vitamin E was observed. We conclude that vitamin C should be given special attention with respect to the relation between diet and cancer.

Topics: Animals; Ascorbic Acid; Body Weight; Carcinoma, Squamous Cell; Diet; Female; Mice; Mice, Hairless; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Skin Neoplasms; Ultraviolet Rays; Vitamin E

A systematic study of vitamin C blood levels in patients with cancer and an evaluation of their modifications when the patients were orally treated with daily large doses of ascorbic acid (5g/day) have been carried out. For excluding any interference on intestinal vitamin C absorption, all patients with digestive tract cancer have been excluded. Our first results concern 24 lung cancer and 35 bladder cancer patients, operable or not, of different sex and age. The study has shown hypovitaminosis C subclinic conditions for the greater part of subjects: in fact the average haematic rate of ascorbic acid approaches to lower level of physiologic range, appearing very low particularly for the younger patients. Periodic haematic dosages of vitamin C of unoperable and operated patients treated with large doses of ascorbic acid, have shown a rapid increase of its blood concentration which frequently has been very over 1500 micrograms%, the higher level of normal range. These high vitamin haematic levels, generally constant during the time, appear usefull in increasing the defence reactions of the cancerous patient.

Topics: Adenocarcinoma; Adult; Age Factors; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Carcinoma; Carcinoma, Squamous Cell; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Urinary Bladder Neoplasms

Previous work in this laboratory has thrown some light on the possible mechanism involved in the anti-tumour activity of ascorbic acid (AA). In order to elucidate this mechanism further, the present studies, involving the effect of AA on protein and RNA synthesis, were carried out. The results obtained in this investigation may support the hypothesis previously put forward for the action of AA on cell proliferation.

Topics: Ascorbic Acid; Carcinoma; Carcinoma, Squamous Cell; Cell Division; Cell Line; Humans; Laryngeal Neoplasms; Mouth Neoplasms; Neoplasm Proteins; RNA, Neoplasm

Topics: Ascorbic Acid; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Skin Neoplasms

The effect of vitamin C on cell proliferation and DNA synthesis was investigated using two tumor cell lines Hep2 and KB. The results show that there was an increase in the ratio of dead to live cells and a decrease in the rate of DNA synthesis. The results also agree with other work carried out on animal experimental models which claimed that vitamin C may be involved in the arrest of neoplastic cell proliferation.

Topics: Ascorbic Acid; Carcinoma, Squamous Cell; Cell Division; Cell Line; Cell Survival; DNA, Neoplasm; Neoplasms, Experimental

Topics: Adenocarcinoma; Adult; Aged; Ascorbic Acid; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Middle Aged; Skin Neoplasms

Topics: Animals; Antioxidants; Ascorbic Acid; Carcinoma, Squamous Cell; Diet; Female; Glutathione; Mice; Neoplasms, Radiation-Induced; Radiation-Protective Agents; Skin Neoplasms; Toluene; Ultraviolet Rays; Vitamin E

Topics: Adult; Aged; Ascorbic Acid; Carcinoma, Squamous Cell; Electron Transport Complex IV; Female; Glycogen; Glycosaminoglycans; Histocytochemistry; Humans; Middle Aged; Uterine Cervical Neoplasms

Topics: Adult; Anemia; Ascorbic Acid; Blood Transfusion; Carcinoma, Squamous Cell; Citrus; Diet; Epistaxis; Female; Gastrointestinal Diseases; Hemoglobins; Humans; Intestinal Absorption; Iron; Leukocytes; Male; Middle Aged; Peptic Ulcer; Pharyngeal Neoplasms; Scurvy; Smoking; Stomatitis, Aphthous

Topics: Animals; Ascorbic Acid; Carcinogens; Carcinoma, Squamous Cell; Humans; Mice; Neoplasms, Experimental; ortho-Aminobenzoates; Oxidation-Reduction; Precancerous Conditions; Urinary Bladder Neoplasms

Topics: Androgens; Antibiotics, Antineoplastic; Antineoplastic Agents; Ascorbic Acid; Azirines; Bronchial Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Cyclophosphamide; Drug Synergism; Fluorouracil; Glucocorticoids; Humans; Hydrazines; Injections, Intramuscular; Injections, Intravenous; Lectins; Lung Neoplasms; Mechlorethamine; Mercaptopurine; Mesothelioma; Methotrexate; Phenylbutazone; Pleural Neoplasms; Thiotepa; Vinblastine

Topics: Ascorbic Acid; Carcinoma, Squamous Cell; Female; Histocytochemistry; Humans; Oxygen Consumption; Uterine Cervical Neoplasms

Topics: Ascorbic Acid; Carcinoma; Carcinoma, Squamous Cell; Female; Humans; Uterine Cervical Neoplasms; Vitamins