ascorbic-acid and Mouth-Neoplasms

In the United States, nearly 44,000 people are diagnosed with oral or pharyngeal cancer annually. The life expectancy for those who are diagnosed have a survival rate of 57% after five years. Among them, oral cancer can be classified as benign or malignant tumors and is diagnosed at several stages in the development: premalignant conditions, premalignant lesions, and malignant cancer. The early signs of oral cancer often go unnoticed by the individual and are often discovered during routine dental examinations. Early detection and treatment may help to increase patient survival rates. The most widely used treatments for oral cancer include surgery, radiation, and chemotherapy-alone or in combination. Preclinical and clinical evidence for the use of green tea, raspberry, asparagus, and cannabis extracts is discussed in this review. Diet changes, supplementation with antioxidants, high-dose vitamin C therapy, and cannabinoid use have been suggested to decrease cancer cell replication and increase chance of remission. Early detection and lifestyle changes, including the use of dietary supplements in at-risk populations, are critical steps in preventing and successfully treating oral cancer. The main evidence for supplement use is currently in cancer prevention rather than treatment. Further research, determination, and mechanism of action for bioactive compounds such as epigallocatechin, epicatechin-3-gallate, and Bowman-Birk inhibitor concentrate, through in vitro, in vivo, and clinical trials need to be completed to support the use of natural products and their effectiveness in preventative care and supporting therapeutic approaches.

Topics: Anthocyanins; Antioxidants; Ascorbic Acid; Asparagus Plant; Cannabinoids; Carotenoids; Catechin; Complementary Therapies; Dietary Supplements; Dose-Response Relationship, Drug; Glycine max; Humans; Lycopene; Mouth Neoplasms; Phytotherapy; Tea

Ascorbic acid or Vitamin C is a potent dietary antioxidant with a double faced character, in that it exhibits a pro-oxidant activity arising from its routine antioxidant property that generates reactive free radicals, which induce cytotoxic effects at pharmacologic concentrations. A systematic review of this effect of ascorbic acid in the oral tumours and normal oral tissues would clearly elucidate the merits or demerits of employing vitamin C in treating the same.. The aim of our systematic review is to critically review the studies reported in literature that have studied the pro-oxidant activity of ascorbic acid as a therapeutic option for treatment of oral neoplasms and its effects on normal oral cells.. Articles were searched in PUBMED, MEDLINE using appropriate key words like "ascorbic acid", "pro-oxidant activity", "treatment", "oral neoplasms". Hand search of Journals was also performed. Articles were reviewed and analysed.. The search strategy included 17 potentially relevant articles for review of which, 12 were in vitro studies; 3 were in vivo animal studies; 1 was in vivo human study and 1 was ex vivo human study. The optimum concentration of ascorbic acid used to produce potential pro-oxidant associated cytotoxic effects was found to be 3-5mM in vitro, 0.88-5mM in vivo animals, 0.5-2mM ex vivo in humans, and the corresponding effects are induction of apoptosis (caspase activation), necrosis, free radical formation, H2O2 generation, and DNA fragmentation. In contrast, the same pro-oxidant concentrations had no effect on the normal cells.. The results of our systematic review show that the pro-oxidant activity of pharmacologic ascorbic acid is a part of its dose-dependent bimodal activity and is a result of the proposed Fenton mechanism. In vitro, animal and ex vivo studies of pharmacologic ascorbic acid (AA) have yielded meritorious results proving vitamin C as an effective cytotoxic agent against oral neoplastic cells with potentially no harming effects on normal cells. However, a shortage of clinical trials and in vivo human studies pertaining to evaluation of anti-tumour activity of vitamin C in tumours of oral cavity remains a lacuna in concluding ascorbic acid as a beneficial therapeutic option in treatment of oral neoplasms.

Topics: Animals; Antineoplastic Agents; Apoptosis; Ascorbic Acid; DNA Fragmentation; Free Radicals; Humans; Hydrogen Peroxide; Mouth Mucosa; Mouth Neoplasms; Necrosis; Oxidants

We reviewed data from six cohort studies and approximately 40 case-control studies on the relation between selected aspects of diet and the risk of oral and pharyngeal cancer. Fruit and vegetables were inversely related to the risk: the pooled relative risk (RR) for high vegetable consumption was 0.65 from three cohort studies on upper aerodigestive tract cancers and 0.52 from 18 case-control studies of oral and pharyngeal cancer; corresponding RRs for high fruit consumption were 0.78 and 0.55. beta-carotene, vitamin C and selected flavonoids have been inversely related to the risk, but it is difficult to disentangle their potential effect from that of fruit and vegetables. Whole grain, but not refined grain, intake was also favorably related to oral cancer risk. The results were not consistent with reference to other foods beverages, and nutrients, but it is now possible to exclude a strong relation between these foods and oral and pharyngeal cancer risk. In western countries, selected aspects of diet may account for 20-25% of oral and pharyngeal cancer, and the population attributable risk increases to 85-95% when tobacco and alcohol consumption are also considered.

Topics: Adult; Ascorbic Acid; beta Carotene; Case-Control Studies; Cohort Studies; Diet; Edible Grain; Female; Flavonoids; Fruit; Humans; Male; Mouth Neoplasms; Pharyngeal Neoplasms; Risk; Risk Factors; Vegetables

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

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

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

Dietary fiber and vitamin C has been reported to play a possible role in tumorigenesis. However, few studies have estimated their association with oral cancer risk. In this project, we investigated the relationship between dietary fiber and vitamin C and oral cancer risk in adults in Southern China.. 382 patients newly diagnosed with oral cancer were matched to 382 hospital derived controls by frequency matching in age and sex. Pre-diagnostic consumption of dietary fiber and vitamin C intake were measured through food frequency questionnaire. Association between nutrients intake and oral cancer risk were evaluated by logistic regression. OR value and 95% confidence interval was calculated.. Intake of dietary fiber and vitamin C was significantly lower in oral cancer patients (8.15 g/day) than in control participants (8.88 g/day). Increased dietary fiber or vitamin C intake was linked to a decreased incidence of OC after adjustment of age, marital status, residence, BMI, occupation, education, tobacco smoking, alcohol consumption and family history of cancer. Dietary intake of fiber and vitamin C were lower in oral cancer patients than in control participants. Dietary fiber and vitamin C were inversely related to risk of oral cancer risk.

Topics: Adult; Ascorbic Acid; Case-Control Studies; Dietary Fiber; Humans; Mouth Neoplasms; Risk Factors

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

Head and neck cancer (HNC) is the seventh most-common type of cancer worldwide. Evidence regarding the potential protective effect of vitamins and carotenoids on HNC is limited and mostly based on case-control studies.. We evaluated the association of intake of dietary vitamins C and E (including supplementation) and the most-common carotenoids (α-carotene, β-carotene, lutein plus zeaxanthin, lycopene, and β-cryptoxanthin) and risk of HNC and HNC subtypes in a large prospective study.. The Netherlands Cohort Study included 120,852 participants. For efficiency reasons, a case-cohort design was used. At baseline in 1986, participants completed a food-frequency questionnaire. A subcohort was randomly selected from the total cohort. After 20.3 y of follow-up, 3898 subcohort members and 415 HNC cases [131 oral cavity cancer (OCCs), 88 oro-/hypopharyngeal cancer (OHPs), and 193 laryngeal cancer cases] were available for analysis. Rate ratios and 95% CIs for highest (quartile 4) compared with lowest (quartile 1) quartiles of vitamin and carotenoid intake were estimated by using the Cox proportional hazards model.. A strong inverse association was shown between vitamin C and HNC overall (multivariable-adjusted rate ratio for quartile 4 compared with quartile 1: 0.39; 95% CI: 0.23, 0.66; P-trend < 0.001), OCC (multivariable-adjusted rate ratio for quartile 4 compared with quartile 1: 0.35; 95% CI: 0.16, 0.77; P-trend < 0.05), and OHPC (multivariable-adjusted rate ratio for quartile 4 compared with quartile 1: 0.29; 95% CI: 0.12, 0.67; P-trend < 0.01). No statistically significant results were shown for vitamin E, α-carotene, β-carotene, lycopene, and lutein plus zeaxanthin. The association of vitamin E and HNC was modified by alcohol status (P-interaction = 0.003) with lower risks in alcohol abstainers.. With this study, we show an inverse association between intake of vitamin C and the incidence of HNC and HNC-subtypes. Future research is recommended to investigate the underlying mechanisms and to confirm our results, which may be promising for the prevention of HNC.

Topics: Aged; Antioxidants; Ascorbic Acid; Carotenoids; Case-Control Studies; Cohort Studies; Diet; Dietary Supplements; Female; Follow-Up Studies; Head and Neck Neoplasms; Humans; Hypopharyngeal Neoplasms; Incidence; Laryngeal Neoplasms; Male; Middle Aged; Mouth Neoplasms; Netherlands; Oropharyngeal Neoplasms; Prospective Studies; Registries; Risk Factors; Vitamin E

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Humans; Mouth Neoplasms; Oxidants

Phyllanthus emblica L. (Euphorbiaceae), a novel natural fruit has long been used as a home remedy by the medical practitioners. In this report, we investigated the chemopreventive effect of P. emblica fruit methanolic extract (PFMet) on oxidant-antioxidant status in hamster buccal pouch carcinogenesis. Buccal pouch carcinoma was induced in hamsters by painting with DMBA (0.5% in mineral oil) on the left buccal pouch three times a week for 14 weeks. By means of HPLC analysis, ascorbic acid (24.13%), gallic acid (10.45%), ellagic acid (1.74%) and quercetin (0.009%) were identified and quantified in the PFMet. The results showed that depleted activities of SOD, CAT and TBARS level and significant elevation were observed in the levels of GSH, vitamin E and activity of GPx in DMBA group of buccal pouch. The level of TBARS was significantly enhanced and the activities of enzymatic (SOD, CAT and GPx) and non-enzymatic (vitamin E, vitamin C and GSH) antioxidants were diminished significantly in plasma of tumor bearing animals. The effects were dose dependent and the above noted parameters were renovated to near normal after supplementation with different doses of PFMet (50, 100 and 200 mg/kg BW). The data obtained in this study clearly indicate that PFMet at a dose of 200mg/kg BW possesses optimum chemopreventive effect against DMBA-induced buccal pouch carcinogenesis.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Ascorbic Acid; Catalase; Cricetinae; Fruit; Glutathione; Glutathione Peroxidase; Male; Mouth Neoplasms; Phyllanthus emblica; Plant Extracts; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vitamin E

Extensive research within the past half-century has indicated that curcumin (diferuloylmethane), a yellow pigment in curry powder, exhibits anti-oxidant, anti-inflammatory, and pro-apoptotic activities. We investigated whether the anti-pre-cancer activities assigned to curcumin are mediated through an anti-oxidant and DNA-protecting mechanism. Patients with oral leukoplakia, oral submucous fibrosis or lichen planus, and healthy individuals (n = 25 for each group) aged 17-50 years were selected. Salivary and serum oxidative markers such as malonaldehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), vitamins C and E were measured just prior to the intake of curcumin, after one week of curcumin intake and following clinical cure of precancerous lesions. Serum and salivary vitamins C and E showed increases, while MDA and 8-OHdG levels showed decreases in patients with oral leukoplakia, submucous fibrosis and lichen planus after intake of curcumin for all categories of precancerous lesions. The changes in these values were observed to be statistically significant after clinical cure of the disease (P < 0.05). The five-point rating scale for pain, as well as lesion size in oral leukoplakia, submucous fibrosis and lichen planus, improved significantly (P < 0.05). In addition, in submucous fibrosis, mouth opening (P < 0.05) recovered significantly. In oral leukoplakia, submucous fibrosis and lichen planus, the levels of serum and salivary vitamins C and E increased significantly, while MDA and 8-OHdG levels decreased after 131(15), 211(17), and 191(18) days, respectively. Values for serum and salivary vitamins C and E showed a significant decrease in oral leukoplakia, submucous fibrosis and lichen planus, in contrast to healthy individuals, but increased significantly in all groups subsequent to curcumin administration after clinical cure of lesions. Based on these results, we can conclude that curcumin mediates its anti-pre-cancer activities by increasing levels of vitamins C and E, and preventing lipid peroxidation and DNA damage.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Adult; Antioxidants; Ascorbic Acid; Biomarkers; Curcumin; Deoxyguanosine; DNA; DNA Damage; Female; Follow-Up Studies; Free Radical Scavengers; Humans; Leukoplakia, Oral; Lichen Planus, Oral; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Mouth Neoplasms; Oral Submucous Fibrosis; Oxidative Stress; Pain Measurement; Precancerous Conditions; Protective Agents; Saliva; Vitamin E; Young Adult

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

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

Case-control studies indicate that vitamins C, E, A and carotenoids decrease risk of oral premalignant lesions (OPLs) and oral cancer, but clinical trials have failed to find protective effects of beta-carotene and suggest that vitamin E may increase risk. The authors prospectively evaluated the association between intake of vitamins C, E, A and carotenoids and incidence of OPL. Participants were 42,340 men in the Health Professionals Follow-up Study who provided information on supplement use and diet every 2-4 years by food frequency questionnaire. The authors confirmed 207 clinically or histopathologically diagnosed OPL events occurring between 1986 and 2002 by medical record review. Multivariate-adjusted relative risks (RR) of OPL were calculated with proportional hazards models. Total intake of vitamin C, vitamin A or carotenoids was not significantly associated with OPL risk. Dietary vitamin C was significantly associated with reduced risk (quintile 5 vs. 1, RR = 0.52, 95% CI 0.31-0.85, p(trend) = 0.04), but no association with supplemental vitamin C was observed. Inverse associations were apparent for beta-cryptoxanthin and alpha-carotene intake. No clear relationship emerged with beta-carotene, lycopene or lutein/zeaxanthin. Vitamin E was associated with increased risk (quintile 5 vs. 1, RR = 1.86, 95% CI 1.06-3.19), particularly among current smokers and with supplemental intake (current-smokers, supplement dose tertile 3 vs. 1, RR = 3.07, 95% CI 1.28-7.34, p(trend) = 0.01). For current smokers, beta-carotene also increased risk. Vitamin C from dietary sources, but not supplements, was associated with a reduced risk of OPL. The observed increased risk for current smokers with high vitamin E or beta-carotene intake should be explored further.

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Carotenoids; Case-Control Studies; Cryptoxanthins; Diet; Humans; Male; Middle Aged; Mouth Neoplasms; Precancerous Conditions; Risk Factors; Smoking; United States; Vitamin A; Vitamin E; Vitamins; Xanthophylls

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

Lipid peroxidation may be involved in cancer and essential nutrients that can scavenge free radicals, such as vitamins E and C, operate in concert. Levels of antioxidant vitamins E and C were estimated in 50 patients with oral cancer and 24 healthy persons served as control. Significantly lower levels of vitamins E and C were observed in oral cancer patients as compared to controls (P < 0.011). Antioxidant nutrients may be utilized to a greater extent in oral cancer patients to counteract free radical-mediated cell disturbances, resulting in a reduction in salivary antioxidant levels.

Topics: Adolescent; Adult; Antioxidants; Ascorbic Acid; Female; Free Radicals; Humans; Lipid Peroxidation; Male; Middle Aged; Mouth Neoplasms; Saliva; Vitamin E

There are about 600 million betel quid (BQ) chewers in the world. BQ chewing is the major risk factor of oral cancer in India, Taiwan, South Africa and numerous other countries. Areca nut (AN) extract, the main component of BQ, exerts cytotoxicity and genotoxicity to several types of cells. In the present study, AN extract induced the unscheduled DNA synthesis (UDS) of gingival keratinocytes (GK). Vitamin C, at concentration of 50 and 200 microg/ml prevented the AN-induced UDS by 41 and 56%, respectively. Glutathione (GSH, 1-3 mM) and N-acetyl-L-cysteine (NAC, 1-3 mM) also protected the AN-induced UDS by 89-100 and 76-90%. These preventive effects were not due to cytotoxicity as analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Deferoxamine (20 and 30 mM), an iron chelator and a free radical scavenger, also prevented AN extract induced UDS of GK by 30-55%. On the contrary, banthocuproine (50-200 microM, a copper chelator) and 1,10-phenanthroline (50, 100 microM, a lipid permeable iron chelator), lacked preventive effects. Specific reactive oxygen species scavengers such as dimethyl-sulfoxide (2%), mannitol (10-20 mM), dimethylthiourea (10-20 mM), pyruvate (10 mM), catalase (200 and 400 U/ml), and superoxide dismutase (50 and 200 U/ml) also lacked these preventive effects. Moreover, higher concentrations of H(2)O(2) (0.5-1 mM) inhibited the basal levels of UDS by 19-37%. Interestingly, NAC, GSH, Vitamin C and deferoxamine cannot prevent the AN-induced morphological changes of GK at similar concentrations. These results reveal that AN extract-induced UDS of GK is associated with free radical reactions. Possibly different ingredients of AN is responsible for genotoxicity and cytotoxicity. Vitamin C, GSH and NAC may be potentially used in the future for chemoprevention of BQ chewing related oral mucosal lesions.

Topics: Antioxidants; Areca; Ascorbic Acid; Cells, Cultured; Chelating Agents; Deferoxamine; DNA; Gingiva; Humans; Keratinocytes; Mouth Neoplasms; Plant Extracts; Sulfhydryl Compounds

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

The relation between selected micronutrients and oral and pharyngeal cancer risk was investigated using data from a case-control study conducted between January 1992 and November 1997 in Italy and Switzerland. Cases were 754 incident, histologically confirmed oral cancers (344 of the oral cavity and 410 of the pharynx) admitted to the major teaching and general hospitals in the study areas. Controls were 1,775 subjects with no history of cancer admitted to hospitals in the same catchment areas for acute, non-neoplastic diseases. Dietary habits were investigated using a validated food-frequency questionnaire. Odds ratios (ORs) were computed after allowance for age, sex, center, education, occupation, body mass index, smoking and drinking habits and non-alcohol energy intake. Micronutrients were analyzed both as continuous variables and in quintiles. In the former case, the unit was set to 1 SD of the distribution of controls. ORs for the continuous analysis were 0.95 for retinol, 0.61 for carotene, 0.91 for lycopene, 0.83 for vitamin D, 0.74 for vitamin E, 0.63 for vitamin C, 0.82 for thiamine, 0.87 for riboflavin, 0.59 for vitamin B6, 0.61 for folic acid, 0.62 for niacin, 0.91 for calcium, 0.88 for phosphorus, 0.65 for potassium, 0.82 for iron, 0.67 for non-alcohol iron and 0.89 for zinc; the 95% confidence interval excluded one for carotene, vitamin C and E, thiamine, vitamin B6, folic acid, niacin, potassium and iron. ORs were similar for the 2 sexes and in strata of age. When the combined intake of vitamins C and E and carotene was considered, the protective effect of each nutrient was more marked or restricted to subjects with low intake of the other 2. The association with vitamin C and carotene was independent of smoking and drinking habits, while that with vitamin E was less evident in those heavily exposed to alcohol or tobacco. In general, the more a micronutrient was correlated to total vegetable and fruit intake, the stronger was its protective effect against oral cancer.

Topics: Adult; Aged; Alcohol Drinking; Ascorbic Acid; Carotenoids; Case-Control Studies; Diet; Female; Humans; Italy; Male; Micronutrients; Middle Aged; Mouth Neoplasms; Pharyngeal Neoplasms; Risk Factors; Smoking; Switzerland; Vitamin E

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

In a clinical trial the effect of chemoprevention with beta-carotene, vitamin E and C on dysplastic tissue was studied. The study included 24 patients with oral leukoplakia and 24 patients after radical resection of a primary oral cancer. There was a reduction of increased cell kinetic parameters like the S-phase portion or the average number of nuclear-organizer regions (NOR) per cell nucleus, a decrease of the micronuclei portion and a normalization of the cytokeratin gene-expression. The general response was 97.5%. Stopping the alcohol and tobacco abuse the effect of the antioxidative vitamins on redifferentiation of the oral mucosa was more intense than by persistance of the alcohol and tobacco abuse, but a long term prevention seems to be ineffective.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Biopsy; Cell Differentiation; Cohort Studies; Drug Therapy, Combination; Humans; Keratins; Leukoplakia; Mouth Mucosa; Mouth Neoplasms; Nucleolus Organizer Region; S Phase; Time Factors; Vitamin E

Photofrin, a photosensitizer used in the photodynamic therapy of cancer, selectively localizes in cellular membranes. Upon exposure to visible light, Photofrin produces singlet oxygen (1O2), which reacts with membrane polyunsaturated fatty acids forming lipid hydroperoxides. Transition metals, such as Fe2+, catalyze the production of cytotoxic free radicals from lipid hydroperoxides. Ascorbate reduces ferric to ferrous iron, further augmenting lipid peroxidation. Therefore, to increase the efficacy of Photofrin photosensitization, we added 20 microM ferrous sulfate and 100 microM ascorbic acid, in an aqueous layer over SCC-25 oral squamous cell carcinoma cells during in vitro illumination. In electron paramagnetic resonance spin trapping experiments, using POBN (alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone), we observed that the presence of this pro-oxidant combination greatly increases the production of membrane-derived lipid free radicals. The effect was time dependent but only partially concentration dependent. Trypan blue dye exclusion demonstrated that this increase in lipid radical formation correlated with cytotoxicity. These observations support the hypothesis that Photofrin photosensitization leads to lipid hydroperoxide formation, which increases the cell's susceptibility to iron-induced Fenton chemistry. The resulting free radical-mediated lipid peroxidation results in cell death. From these data we hypothesize that the efficacy of photodynamic therapy of superficial cancer might be increased by the topical application of the pro-oxidant combination of iron and ascorbate. Furthermore, their use will probably allow lower doses of Photofrin without compromising antitumor effect.

Topics: Antineoplastic Agents; Ascorbic Acid; Dihematoporphyrin Ether; Drug Interactions; Ferrous Compounds; Free Radicals; Humans; Mouth Neoplasms; Neoplasms, Squamous Cell; Photosensitizing Agents; Tumor Cells, Cultured

Vitamin C is an essential nutrient whose protective influence is carcinogenesis has been reported frequently, suggesting that vitamin C inhibits the formation of some carcinogens and decreases the incidence and delays of the neoplastic lesions. However, the mechanisms by which this occurs are unknown. In this study, the water soluble carcinogen 4-nitroquinoline-1-oxide (4NQO) has been used to induce a high yield of tumours in the oral cavity either singly or in combination with tobacco. Since the mucosa of rats is less susceptible to carcinogens than the hamster cheek pouch, the hamster cheek pouch has been used to study the influence of vitamin C on 4NQO-induced oral malignancy. The aim of this study was to determine whether topically applied vitamin C had an effect on the oral carcinogenesis induced by application of 4NQO. Similarly, an attempt was made to study the modulating effect of vitamin C on the histopathological and ultrastructural changes during the neoplastic process in the hamster. Vitamin C appeared to delay tumour induction and had other protective effects against neoplasia.

Topics: 4-Nitroquinoline-1-oxide; Animals; Ascorbic Acid; Carcinogens; Cell Transformation, Neoplastic; Cheek; Cricetinae; Mesocricetus; Microscopy, Electron; Mouth Neoplasms; Nicotiana; Plants, Toxic

Wistar Shionogi rats of the (od/od) substrain with the osteogenic disorder are unable to synthesize L-ascorbic acid (L-AA) and appear to be an appropriate animal model for studying the effect of L-AA in carcinogenesis. To determine the minimal L-AA requirements of these animals for prolonged survival in a satisfactory physical condition during experimentation, four concentrations of L-AA (0.33 g/l, 0.67 g/l, 1.67 g/l and 3.33 g/l) were administered via drinking water to four groups of animals (n = 2). Their water intake per cage was recorded three times weekly and the plasma L-AA levels were determined at the start, after 2, 4, 8 and 12 weeks and at the termination of the experiment. To simulate the procedures to be undertaken in oral mucosal carcinogenesis experiments, the animals were gently restrained and a designated amount of sterile NaCl was applied to the palatal mucosa three times a week for 26 weeks. The L-AA supplement group with the lowest concentration (0.33 g/l L-AA) achieved mean plasma levels of 7 +/- 1.38 microM, approximately one-eighth that of the normal level (mean plasma L-AA level in outbred Wistar rats was found to be 58 +/- 3 microM) whilst those in the higher supplement group (3.33 g/l L-AA) achieved a mean of 18 +/- 1.25 microM. All of the animals employed in the present study survived for 26 weeks and showed no clinical signs of L-AA deficiency during this period.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Male; Mouth Neoplasms; Nutritional Requirements; Osteogenesis; Point Mutation; Rats; Rats, Mutant Strains; Rats, Wistar

This combined analysis of data from three large case-control studies of oral cancer confirms the important effect of tobacco in the aetiology of the disease. The studies have been conducted in the United States, Italy and China and results for risks associated with tobacco smoking were generally consistent across centres, while those for alcohol were not; increased risks amongst alcohol drinkers were evident in two centres but not in the study conducted in Turin, Italy. In addition, the combined analysis had large enough numbers to analyse the risk of tobacco consumption in non-drinkers. In females these showed increased risks while in males the effect of tobacco alone was weaker. Given the popularity of tobacco smoking, and its consequent high attributable risk in terms of oral cancer it is reassuring, in terms of public health, that cessation will result in a substantial reduction in risk; a 30% reduction in risk for those stopping smoking between 1 and 9 years, and a 50% reduction for those stopping more than 9 years. Although encouraging smokers to stop should be the principal aim, decreases in risk for everyone could be achieved by encouraging high fruit and vegetable consumption.

Topics: Adult; Age Distribution; Aged; Alcohol Drinking; Ascorbic Acid; Case-Control Studies; China; Diet; Energy Intake; Female; Humans; Italy; Male; Middle Aged; Mouth Neoplasms; New York; Risk Factors; Sex Distribution; Smoking

Previous studies have shown that beta-carotene and alpha-tocopherol can act synergistically to inhibit the growth of experimentally induced oral cancer. The initial studies on the synergistic anticancer activity of antioxidants have been extended to include reduced glutathione and ascorbic acid. Sixty male hamsters (4-5 wks old) were divided into six equal groups. Groups 1-6 were treated with 7,12-dimethylbenz[a]anthracene (DMBA) (0.5% solution). Group 2 received a mixture containing equal amounts of beta-carotene, dl-alpha-tocopherol (vitamin E), glutathione, and l-ascorbic acid (vitamin C) (12.5 micrograms) delivered orally by pipette. Groups 3-6 were treated with beta-carotene alone (50 micrograms), vitamin E alone (50 micrograms), glutathione (50 micrograms) alone, and vitamin C alone (50 micrograms). Animals were euthanized at 12 and 14 weeks. Tumors were counted and measured, and tumor burden was calculated for each experimental group. The mixture of antioxidants significantly reduced tumor burden, whereas the beta-carotene, vitamin E, and reduced glutathione treatments also reduced tumor burden. beta-Carotene and glutathione provided greater levels of chemoprevention than vitamin E as single agents. In contrast, vitamin C treatment produced no antitumor effect but increased tumor burden by Week 14. This mixture of antioxidants produced a significant synergistic chemoprevention of oral cancer.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Administration, Oral; Animals; Ascorbic Acid; beta Carotene; Carotenoids; Cricetinae; Drug Combinations; Drug Synergism; Glutathione; Leukoplakia; Male; Mesocricetus; Mouth Neoplasms; Vitamin E

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

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

This study reports the mechanism of involvement of vitamin C in the pathogenesis of induced oral carcinogenesis in the hamster cheek pouch epithelium. This site was exposed to either DMBA singly or in combination with vitamin C or DMBA for 7 weeks followed by only vitamin C till tumour induction. Macroscopically, vitamin C reduces the epithelial tumour incidence in the hamster cheek pouch. Microscopically tumours induced by DMBA alone were well differentiated squamous carcinomas in all the animals, whereas those induced by DMBA plus vitamin C were papillary epidermoid carcinomas with minimal invasion. These observations suggest that vitamin C is capable of restricting the growth of the initiated cells and does not allow the invasion of the subepithelium. The mechanism of action of vitamin C in the process of restricting growth and invagination was clearly shown in ultrastructural pathology too. In vitamin C exposed tumours the dermal epidermal junction of the cheek pouch epithelium maintains basement membrane integrity, with the presence of cellular organelles and cytoskeletal structure of the cells.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Ascorbic Acid; Cricetinae; Incidence; Male; Mesocricetus; Mouth Neoplasms

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

Topics: Alcohol Drinking; Ascorbic Acid; Dentures; Humans; Mouth Neoplasms; Neoplasms, Radiation-Induced; Nicotiana; Plants, Toxic; Risk Factors; Vitamin A

Topics: Ascorbic Acid; Diet; Dose-Response Relationship, Drug; Fruit; Gastrointestinal Neoplasms; Humans; Lung Neoplasms; Male; Mouth Neoplasms; Risk; Vegetables; Vitamin A

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: Adult; Ascorbic Acid; Breast Neoplasms; Child; Female; Humans; Leukocytes; Lung Neoplasms; Mouth Neoplasms; Neoplasms; Rectal Neoplasms; Skin Neoplasms; Urinary Bladder Neoplasms; Uterine Cervical Neoplasms

Topics: Animals; Ascorbic Acid; Biotransformation; Carcinoma; Catechols; Cell Division; Cell Line; Chromatography, Thin Layer; Depression, Chemical; Ethanol; Fibroblasts; Flavonoids; Glutathione; Haplorhini; Humans; Macaca; Mouth Neoplasms; Oxidation-Reduction; Oxygen Consumption; Quinones; Rutin; Spectrophotometry, Ultraviolet; Stimulation, Chemical; Time Factors

Topics: Acetaminophen; Adolescent; Adult; Aged; Analgesics; Ascorbic Acid; Female; Humans; Male; Middle Aged; Mouth Diseases; Mouth Neoplasms

Topics: Ascorbic Acid; Blood; Chronic Disease; Humans; Leukocytes; Mouth Neoplasms; Research; Vitamins