ascorbic-acid and Carcinoma

Topics: Adenoma; Ascorbic Acid; Carcinoma; Cytodiagnosis; Glycogen; Glycosaminoglycans; Goiter, Nodular; Histocytochemistry; Humans; Hyperplasia; Karyometry; Precancerous Conditions; Thyroid Gland; Thyroid Neoplasms; Thyroiditis, Autoimmune

The objective of this study, in addition to confirming that therapy with 131I causes oxidative stress, was to evaluate the effect of supplementation with vitamins C and E and selenium on this phenomenon by measuring plasma 8-epi-PGF2a, a marker of lipid peroxidation.. Forty patients with thyroid cancer submitted to thyroidectomy, who received 3.7 GBq 131I after levothyroxine withdrawal, were selected; 20 patients did not receive (control group) and 20 patients received (intervention group) daily supplementation consisting of 2000 mg vitamin C, 1000 mg vitamin E and 400 µg selenium for 21 days before 131I. Plasma 8-epi-PGF2a was measured immediately before and 2 and 7 days after 131I.. A significant increase in plasma 8-epi-PGF2a after 131I was observed in the two groups. The concentrations of 8-epi-PGF2α were significantly higher in the control group before and 2 and 7 days after 131I. The percentage of patients with elevated 8-epi-PGF2α was also significantly higher in the control group before and after 131I. Furthermore, the increase (percent) in 8-epi-PGF2α was significantly greater in the control group (average of 112.3% versus 56.3%). Only two patients (10%) reported side effects during supplementation.. Ablation with 131I causes oxidative stress which can be minimized by the use of antioxidants.

Topics: Adult; Analysis of Variance; Antioxidants; Ascorbic Acid; Carcinoma; Dietary Supplements; Dinoprost; Female; Humans; Iodine Radioisotopes; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Prospective Studies; Reproducibility of Results; Selenium; Thyroid Neoplasms; Thyroidectomy; Thyroxine; Time Factors; Treatment Outcome; Vitamin E; Young Adult

Nanoparticles can potentially cause adverse effects on cellular and molecular level. The present study aimed to investigate the histopathological changes and DNA damage effects of magnetite nanoparticles (MNPs) on female albino mice model with Ehrlich solid carcinoma (ESC). Magnetite nanoparticles coated with L-ascorbic acid (size ~ 25.0 nm) were synthesized and characterized. Mice were treated with MNPs day by day, intraperitoneally (IP), intramuscularly (IM), or intratumorally (IT). Autopsy samples were taken from the solid tumor, thigh muscle, liver, kidney, lung, spleen, and brain for assessment of iron content, histopathological examination, and genotoxicity using comet assay. The liver, spleen, lung, and heart had significantly higher iron content in groups treated IP. On the other hand, tumor, muscles, and the liver had significantly higher iron content in groups treated IT. MNPs induced a significant DNA damage in IT treated ESC. While a significant DNA damage was detected in the liver of the IP treated group, but no significant DNA damage could be detected in the brain. Histopathological findings in ESC revealed a marked tumor necrosis, 50% in group injected IT but 40% in group injected IP and 20% only in untreated tumors. Other findings include inflammatory cell infiltration, dilatation, and congestion of blood vessels of different organs of treated groups in addition to appearance of metastatic cancer cells in the liver of non-treated tumor group. MNPs could have an antitumor effect but it is recommended to be injected intratumorally to be directed to the tumor tissues and reduce its adverse effects on healthy tissues.

Topics: Animals; Ascorbic Acid; Carcinoma; DNA Damage; Female; Iron; Magnetite Nanoparticles; Mice; Tissue Distribution

Vegetable and fruit consumption may have a protective effect against several types of cancers. However, the effect on biliary cancers is unclear. We investigated the association of vegetable/fruit consumption with the risks of gallbladder cancer (GBC), intrahepatic bile duct cancer (IHBDC) and extrahepatic bile duct cancer (EHBDC) in a population-based prospective cohort study in Japan. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazard model, and the exposure level was categorized into quartiles, with the lowest group used as the reference. A total of 80,371 people aged 45 to 74 years were enrolled between 1995 and 1999, and followed up for 1,158,632 person-years until 2012, during which 133 GBC, 99 IHBDC, and 161 EHBDC cases were identified. Increased consumption of total vegetable and fruit was significantly associated with a decreased risk of EHBDC (HR = 0.49; 95% CI: 0.29-0.81 for the highest group; p trend = 0.005). From the analysis of relevant nutrients, significantly decreased risk of EHBDC was associated with folate and insoluble fiber (HR = 0.48, 0.53; 95% CI: 0.28-0.85, 0.31-0.88 for the highest group; p trend = 0.010, 0.023; respectively), and a significant trend of decreased EHBDC risk associated with vitamin C was observed (p trend = 0.029). No decreased risk of GBC and IHBDC was found. Our findings suggest that increased vegetable/fruit consumption may decrease a risk of EHBDC, and folate, vitamin C, and insoluble fiber might be key contributors to the observed protective effect.

Topics: Adult; Alcohol Drinking; Ascorbic Acid; Bile Duct Neoplasms; Carcinoma; Cholelithiasis; Comorbidity; Diabetes Mellitus; Diet; Dietary Fiber; Female; Folic Acid; Follow-Up Studies; Fruit; Gallbladder Neoplasms; Hepatitis, Viral, Human; Humans; Japan; Life Style; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Smoking; Surveys and Questionnaires; Vegetables

Sulindac has anti-neoplastic properties against colorectal cancers; however, its use as a chemopreventive agent has been limited due to toxicity and efficacy concerns. Combinatorial treatment of colorectal cancers has been attempted to maximize anti-cancer efficacy with minimal side effects by administrating NSAIDs in combination with other inhibitory compounds or drugs such as l-ascorbic acid (vitamin C), which is known to exhibit cytotoxicity towards various cancer cells at high concentrations. In this study, we evaluated a combinatorial strategy utilizing sulindac and vitamin C. The death of HCT116 cells upon combination therapy occurred via a p53-mediated mechanism. The combination therapeutic resistance developed in isogenic p53 null HCT116 cells and siRNA-mediated p53 knockdown HCT116 cells, but the exogenous expression of p53 in p53 null isogenic cells resulted in the induction of cell death. In addition, we investigated an increased level of intracellular ROS (reactive oxygen species), which was preceded by p53 activation. The expression level of PUMA (p53-upregulated modulator of apoptosis), but not Bim, was significantly increased in HCT116 cells in response to the combination treatment. Taken together, our results demonstrate that combination therapy with sulindac and vitamin C could be a novel anti-cancer therapeutic strategy for p53 wild type colon cancers.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; Ascorbic Acid; Carcinoma; Colonic Neoplasms; Combined Modality Therapy; Dietary Supplements; Drug Resistance, Neoplasm; Food-Drug Interactions; Gene Expression Regulation, Neoplastic; HCT116 Cells; Humans; Osmolar Concentration; Oxidants; Proto-Oncogene Proteins; Reactive Oxygen Species; RNA Interference; Sulindac; Tumor Suppressor Protein p53

To investigate the effects of dietary vitamin C and foods containing vitamin C on gastric cancer risk.. Our study included 830 control subjects and 415 patients. Data regarding demographics, medical history, and lifestyle, including dietary and nutrient intake, were collected using reliable self-administered questionnaires. Dietary intake information was collected from the participants using a food frequency questionnaire that has been previously reported as reliable and valid. A rapid urease test and a histological evaluation were used to determine the presence of Helicobacter pylori (H. pylori) infection. Twenty-three vitamin C-contributing foods were selected, representing over 80% of the cumulative vitamin C contribution.. In analyses adjusted for first-degree family history of gastric cancer, education level, job, household income, smoking status, and regular exercise, an inverse association between vitamin C intake and gastric cancer risk was observed for the highest (≥ 120.67 mg/d) vs the lowest (< 80.14 mg/d) intake category [OR (95%CI): 0.64 (0.46-0.88)], with a significant trend across the three intake categories (P = 0.007). No protective effect of vitamin C was detected after stratification by gender. No effect of vitamin C intake on the gastric cancer incidence was found in either men or women infected with H. pylori. Vitamin C-contributing foods, including cabbage [0.45 (0.32-0.63), 0.50 (0.34-0.75), 0.45 (0.25-0.81)], strawberries [0.56 (0.40-0.78), 0.49 (0.32-0.74), 0.52 (0.29-0.93)], and bananas [0.40 (0.29-0.57), 0.41 (0.27-0.62), 0.34 (0.19-0.63)], were protective factors against the risk of gastric cancer based on the results of the overall adjusted analyses and the results for men and women, respectively.. A protective effect of vitamin C and vitamin C-contributing foods against gastric cancer was observed. Further studies using larger sample sizes are required to replicate our results.

Topics: Adult; Ascorbic Acid; Carcinoma; Case-Control Studies; Diet; Dietary Carbohydrates; Energy Intake; Female; Fruit; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Male; Middle Aged; Protective Factors; Republic of Korea; Risk Factors; Solanum tuberosum; Stomach Neoplasms; Surveys and Questionnaires

In vitro antiproliferative effects of selenium nanoparticles (nanoSe(0), 10-40 μmol/L) on HeLa (human cervical carcinoma) cells and MDA-MB-231 (human breast carcinoma) cells were examined by optical microscopic inspection and MTT assay in the present study. The nanoSe(0) effectively inhibited the growth of MDA-MB-231 cells and HeLa cells in a dose-dependent manner. The morphology analysis with atomic force microscope showed that the HeLa cells treated with 10 μmol/L nanoSe(0) were rough and shrunken with truncated lamellipodia at terminal part of the cells. Flow cytometric analysis demonstrated that HeLa cells were arrested at S phase of the cell cycle after exposed to nanoSe(0) (10 μmol/L). Taken together, our results suggested that nanoSe(0) may be more helpful in cancer chemoprevention as a potential anticancer drug.

Topics: Anticarcinogenic Agents; Apoptosis; Ascorbic Acid; Breast Neoplasms; Carcinoma; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Female; Flow Cytometry; HeLa Cells; Humans; Microscopy, Atomic Force; Nanoparticles; S Phase; Selenium Compounds; Selenium Oxides; Uterine Cervical Neoplasms

Ascorbic acid demonstrates a cytotoxic effect by generating hydrogen peroxide, a reactive oxygen species (ROS) involved in oxidative cell stress. A panel of eleven human cancer cell lines, glioblastoma and carcinoma, were exposed to serial dilutions of ascorbic acid (5-100 mmol/L). The purpose of this study was to analyse the impact of catalase, an important hydrogen peroxide-detoxifying enzyme, on the resistance of cancer cells to ascorbic acid mediated oxidative stress.. Effective concentration (EC(50)) values, which indicate the concentration of ascorbic acid that reduced the number of viable cells by 50%, were detected with the crystal violet assay. The level of intracellular catalase protein and enzyme activity was determined. Expression of catalase was silenced by catalase-specific short hairpin RNA (sh-RNA) in BT-20 breast carcinoma cells. Oxidative cell stress induced apoptosis was measured by a caspase luminescent assay.. The tested human cancer cell lines demonstrated obvious differences in their resistance to ascorbic acid mediated oxidative cell stress. Forty-five percent of the cell lines had an EC(50) > 20 mmol/L and fifty-five percent had an EC(50) < 20 mmol/L. With an EC(50) of 2.6-5.5 mmol/L, glioblastoma cells were the most susceptible cancer cell lines analysed in this study. A correlation between catalase activity and the susceptibility to ascorbic acid was observed. To study the possible protective role of catalase on the resistance of cancer cells to oxidative cell stress, the expression of catalase in the breast carcinoma cell line BT-20, which cells were highly resistant to the exposure to ascorbic acid (EC(50): 94,9 mmol/L), was silenced with specific sh-RNA. The effect was that catalase-silenced BT-20 cells (BT-20 KD-CAT) became more susceptible to high concentrations of ascorbic acid (50 and 100 mmol/L).. Fifty-five percent of the human cancer cell lines tested were unable to protect themselves against oxidative stress mediated by ascorbic acid induced hydrogen peroxide production. The antioxidative enzyme catalase is important to protect cancer cells against cytotoxic hydrogen peroxide. Silenced catalase expression increased the susceptibility of the formerly resistant cancer cell line BT-20 to oxidative stress.

Topics: Antineoplastic Agents; Antioxidants; Apoptosis; Ascorbic Acid; Breast Neoplasms; Carcinoma; Catalase; Cell Line, Tumor; Gene Silencing; Glioblastoma; Humans; Hydrogen Peroxide; Neoplasms; Oxidants; Oxidative Stress; RNA, Small Interfering; Vitamins

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

Conventional treatment approaches have had little impact on the course of pancreatic cancer, which has the highest fatality rate among cancers. Gemcitabine, the primary therapeutic agent for pancreatic carcinoma, produces minimal survival benefit as a single agent. Therefore, numerous efforts have focused on gemcitabine combination treatments. Using a ratio design, this study established that combining pharmacologically achievable concentrations of ascorbate with gemcitabine resulted in a synergistic cytotoxic response in eight pancreatic tumor cell lines. Sensitization was evident regardless of inherent gemcitabine resistance and epithelial-mesenchymal phenotype. Our analysis suggested that the promiscuous oxidative actions of H(2)O(2) derived from pharmacologic ascorbate can culminate in synergism independent of the cancer cell's underlying phenotype and resistance to gemcitabine monotherapy. Gemcitabine-ascorbate combinations administered to mice bearing pancreatic tumor xenografts consistently enhanced inhibition of growth compared to gemcitabine alone, produced 50% growth inhibition in a tumor type not responsive to gemcitabine, and demonstrated a gemcitabine dose-sparing effect. These data support the testing of pharmacologic ascorbate in adjunctive treatments for cancers prone to high failure rates with conventional therapeutic regimens, such as pancreatic cancer.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Carcinoma; Cell Line, Tumor; Deoxycytidine; Drug Evaluation, Preclinical; Drug Resistance, Neoplasm; Drug Synergism; Female; Gemcitabine; Humans; Mice; Mice, Nude; Pancreatic Neoplasms; Xenograft Model Antitumor Assays

Two popular complementary, alternative, and integrative medicine therapies, high-dose intravenous ascorbic acid (AA) and intravenous glutathione (GSH), are often coadministered to cancer patients with unclear efficacy and drug-drug interaction. In this study we provide the first survey evidence for clinical use of iv GSH with iv AA. To address questions of efficacy and drug-drug interaction, we tested 10 cancer cell lines with AA, GSH, and their combination. The results showed that pharmacologic AA induced cytotoxicity in all tested cancer cells, with IC(50) less than 4 mM, a concentration easily achievable in humans. GSH reduced cytotoxicity by 10-95% by attenuating AA-induced H(2)O(2) production. Treatment in mouse pancreatic cancer xenografts showed that intraperitoneal AA at 4 g/kg daily reduced tumor volume by 42%. Addition of intraperitoneal GSH inhibited the AA-induced tumor volume reduction. Although all treatments (AA, GSH, and AA+GSH) improved survival rate, AA+GSH inhibited the cytotoxic effect of AA alone and failed to provide further survival benefit. These data confirm the pro-oxidative anti-cancer mechanism of pharmacologic AA and suggest that AA and GSH administered together provide no additional benefit compared with AA alone. There is an antagonism between ascorbate and glutathione in treating cancer, and therefore iv AA and iv GSH should not be coadministered to cancer patients on the same day.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Ascorbic Acid; Carcinoma; Drug Evaluation, Preclinical; Drug Interactions; Female; Glutathione; HeLa Cells; Humans; Infusions, Parenteral; Injections, Intravenous; Mice; Mice, Nude; Pancreatic Neoplasms; Tumor Burden; Xenograft Model Antitumor Assays

Ascorbate and menadione (Apatone) in a ratio of 100:1 kills tumor cells by autoschizis. In this study, vitamin-induced changes in nucleolar structure were evaluated as markers of autoschizis. Human bladder carcinoma (T24) cells were overlain with vitamins or with culture medium. Supernatants were removed at 1-hr intervals from 1 to 4 hr, and the cells were washed with PBS and prepared for assay. Apatone produced marked alterations in nucleolar structure including redistribution of nucleolar components, formation of ring-shaped nucleoli, condensation and increase of the proportion of perinucleolar chromatin, and the enlargement of nucleolar fibrillar centers. Immunogold labeling of the nucleolar rRNA revealed a granular localization in treated and sham-treated cells, and immunogold labeling of the rDNA revealed a shift from the fibrillar centers to the condensed perinucleolar chromatin. Fibrillarin staining shifted from the fibrillar centers and adjacent regions to a more homogeneous staining of the entire nucleolus and was consistent with the percentage of autoschizic cells detected by flow cytometry. Because autoschizis entails sequential reactivation of DNase I and DNase II, and because the fibrillarin redistribution following DNase I and Apatone treatment is identical, it appears that the nucleolar and fibrillarin changes are markers of autoschizis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Carcinoma; Cell Line, Tumor; Cell Nucleolus; Chromosomal Proteins, Non-Histone; Humans; Urinary Bladder Neoplasms; Vitamin K; Vitamin K 3

Effects of ascorbic acid on calcium homeostasis of human laryngeal carcinoma cells were studied. Intracellular concentration of free calcium and intracellular pH were measured by fluorescent analysis. Ascorbic acid in concentrations of 3-10 mM caused pH drop and sharply increased concentrations of free Ca ions in HEp-2 cells. Intracellular concentration of free Ca ions resulted from Ca ion release from the thapsigargin-sensitive Ca depots.

Topics: Antioxidants; Ascorbic Acid; Calcium; Calcium Signaling; Carcinoma; Cell Line, Tumor; Dose-Response Relationship, Drug; Enzyme Inhibitors; Extracellular Space; Fluorescence; Humans; Hydrogen Peroxide; Hydrogen-Ion Concentration; Intracellular Space; Laryngeal Neoplasms; Oxidants; Thapsigargin; Time Factors

Mycoplasma hyorhinis (M. hyorhinis) exerts multiple effects on cell metabolisms including apoptosis mediated by their endonucleases and nitric oxide production in vitro. Although AsA is preferable to health in general because of its reactive oxygen species scavenging activity, we found that in a human carcinoma cell line AZ-521 infected with M. hyorhinis, apoptosis was enhanced by addition of L-ascorbic acid (AsA) to the cell cultures. No significant differences were evident between the AZ-521 cells with and without AsA (AsA-) after 24 hr of incubation in the mitochondrial fluorescence. M. hyorhinis-infected AZ-521 cells treated with AsA (AsA +) have developed distinct DNA ladders as compared to the control cells AsA- after 24 hr of incubation. Marked cytopathic effects were rather apparent in AsA-treated cells than in control cells AsA- after 24 hr. Our data demonstrate that AsA addition to cell cultures enhances apoptosis induced by M. hyorhinis infection. We suggest that the presence of another external apoptotic pathway by M. hyorhinis infection.

Topics: Apoptosis; Ascorbic Acid; Carcinoma; Cell Line, Tumor; DNA Fragmentation; Dose-Response Relationship, Drug; Humans; Mycoplasma hyorhinis; Stomach Neoplasms

Feulgen and actin-phalloidin staining as well as gel electrophoresis have been employed in conjunction with cell ultrastructure to describe the effects of 1-, 2-, and 4-hr ascorbate (VC), menadione (VK(3)), and ascorbate:menadione (VC:VK(3)) treatments on the T24 human bladder carcinoma cell line. T24 cells exposed to VC alone display blebs and other superficial membrane defects related to membrane alterations and to superficial cytoskeleton changes. VK(3) treatment damages the cell nucleus and organelles, leads to the redistribution of the organelles in the perikaryon as a consequence of cytoskeletal damage, and results in cytoplasmic self-excisions. After VC:VK(3) treatment, the cells show exaggerated alterations characteristic of each vitamin treatment alone, including damaged mitochondria, self-excision of organelle-free pieces of cytoplasm, and extrusion of the perikaryon containing a nucleus surrounded by the damaged organelles. The nuclear envelope appears intact and contains chromatin that decondenses and dissipates. During the cellular demise that concludes with apparent karyolysis, the cells significantly decrease their size and alter their shape. However, the cisterns of rough endoplasmic reticulum are undamaged, but may become dilated. Since the cellular phenomena leading to cell death differ morphologically from apoptosis and necrosis, but entail self-cutting without nuclear bodies, this new form of cell death was called autoschizis. In addition, gel electrophoresis and Feulgen staining demonstrate that autoschizis is accompanied by random DNA degeneration.

Topics: Ascorbic Acid; Carcinoma; Cell Death; Cell Line, Tumor; Densitometry; DNA Fragmentation; Drug Synergism; Electrophoresis; Histocytochemistry; Humans; Rosaniline Dyes; Urinary Bladder Neoplasms; Vitamin K 3

Curative potential of riboflavin, niacin and ascorbic acid against tamoxifen mediated endometrial carcinoma was established by studies on carbohydrate metabolizing enzymes. The enzymes investigated were glycolytic enzymes namely, hexokinase; aldolase; phosphoglucoisomerase and the gluconeogenic enzymes namely, glucose-6-phosphatase and fructose-1, 6-biphosphatase in endometrial carcinoma bearing rats. A significant increase in glycolytic enzymes and a subsequent decrease in gluconeogenic enzymes were observed in plasma, liver and kidney of endometrial carcinoma animals. The administration of riboflavin (45 mg/kg bw/day), niacin (100 mg/kg bw/day) and ascorbic acid (200 mg/kg bw/day) along with tamoxifen (45 mg/kg bw/day) caused a significant decrease in the activity of glycolytic enzymes and a significant increase in the activities of gluconeogenic enzymes to near normal levels in experimental animals. Our results suggest that riboflavin, niacin and ascorbic acid have potential combination therapy against tamoxifen mediated secondary endometrial carcinoma in experimental rats. However, there were no deleterious side effects observed in combinants alone treated animals.

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Carbohydrate Metabolism; Carcinoma; Drug Evaluation, Preclinical; Endometrial Neoplasms; Female; Neoplasm Metastasis; Niacin; Rats; Rats, Sprague-Dawley; Riboflavin; Tamoxifen

We evaluated the antitumor effects of vitamins C and K3 for human urothelial carcinoma and the potential use of the combination of vitamins C plus K3 as a sensitizing agent for conventional chemotherapy for urothelial carcinoma.. The antiproliferative and apoptotic effects of vitamin C alone, vitamin K3 alone, vitamins C plus K3, gemcitabine alone and gemcitabine plus vitamins C plus K3 were assessed in vitro by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, propidium iodide staining and flow cytometry. For in vivo studies we implanted UMUC-14 tumorigenic urothelial carcinoma cells into the subcutis of nude mice. One week later we treated 10 mice each with saline (control), vitamins C plus K3, gemcitabine or gemcitabine plus vitamins C plus K3. Treatment was continued for 4 weeks, followed by necropsy. Tumor volume was measured and tumor kinetics were established. Apoptosis and proliferation were evaluated in tumor sections using immunohistochemistry and TUNEL assay.. Vitamins C plus K3 induced cytostasis and caused apoptosis to a greater degree than either vitamin alone (p < 0.05). Vitamins C plus K3 also substantially augmented the effects of gemcitabine in vitro. There were 32.3% apoptosis with gemcitabine plus vitamins C plus K3, 5.3% with gemcitabine alone and 15.8% with vitamins C plus K3 alone (p < 0.05). In vivo tumor growth was substantially inhibited by gemcitabine plus vitamins C plus K3 compared with that in the control or for either agent alone. Mean tumor weight and growth rate in the gemcitabine plus vitamins C plus K3 group (237 mg and 11.3 mm3 daily) were decreased compared with those in the control (530 mg and 34.3 mm3 daily), and those for vitamins C plus K3 alone (490 mg and 25.2 mm3 daily) and gemcitabine alone (400 mg and 21.3 mm3 daily) (p < 0.05).. Vitamins C and K3 have significant antiproliferative and apoptotic effects when used in combination. This combination enhances the efficacy of gemcitabine against bladder cancer in vivo.

Topics: Animals; Antimetabolites, Antineoplastic; Apoptosis; Ascorbic Acid; Carcinoma; Cell Culture Techniques; Cell Line, Tumor; Cell Proliferation; Deoxycytidine; Gemcitabine; Humans; Male; Mice; Mice, Inbred BALB C; Urinary Bladder Neoplasms; Urothelium; Vitamin K 3; Vitamins

Initiation activity of phenylethyl isothiocyanate (PEITC) was examined in a two-stage urinary bladder carcinogenesis model. Male 6-week-old Fischer 344 rats were fed diet containing 0.1% PEITC for 12 or 24 weeks, with or without subsequent administration of 5% sodium l-ascorbate (Na-AsA) in diet until week 48, or for the entire experimental period. After 12 weeks of PEITC-treatment, both simple hyperplasia and papillary or nodular (PN) hyperplasia had developed in all animals, but the majority of these lesions had disappeared at week 48, irrespective of the Na-AsA-treatment. The same lesions after 24 weeks of PEITC-treatment had progressed to dysplasia and carcinoma, in a small number of cases by week 48 (6% in incidence for each lesion), but enhancement by the Na-AsA-treatment was evident only with simple hyperplasias (from 56 to 100% in incidence) and PN hyperplasias (from 19 to 56%). The results suggest a limited initiation activity of PEITC with induction of irreversible lesions by 24 weeks of exposure.

Topics: Animals; Ascorbic Acid; Body Weight; Carcinoma; Diet; Hyperplasia; Isothiocyanates; Male; Rats; Rats, Inbred F344; Urinary Bladder Neoplasms

The confluence-dependent resistance of human larynx carcinoma HEp-2 cells to hydrogen peroxide and a new antitumor drug based on the combination of vitamins C and B12b was studied. It was found that this resistance in growing cells is suppressed by the disruption of intercellular contacts by EGTA and is related neither to the activity of P-glycoprotein nor to the content of intracellular glutathione and the activities of glutathione S-transferases, glutathione peroxidase and glutathionine reductase. Here we showed that the level of expression of the small heat shock protein hsp27, which is known to protect cells from a variety of stresses associated with apoptosis, in growing confluent cells both in the presence and absence of the vitamins B12b and C is much higher (about 20-25 times) than in non-confluent cells. Taken together, the results suggest that the confluence-dependent resistance of cells to the combination of vitamins C and B12b and to hydrogen peroxide is mediated by hsp27 overexpression, which is activated via cell-cell adhesion.

Topics: Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; ATP Binding Cassette Transporter, Subfamily B, Member 1; Carcinoma; Cell Adhesion; Cell Communication; Cell Culture Techniques; Cell Division; Drug Resistance, Neoplasm; Egtazic Acid; Glutathione; Heat-Shock Proteins; HSP27 Heat-Shock Proteins; Humans; Hydrogen Peroxide; Hydroxocobalamin; Laryngeal Neoplasms; Molecular Chaperones; Neoplasm Proteins; Tumor Cells, Cultured

Vitamin C (ascorbate) is toxic to tumour cells, and has been suggested as an adjuvant cancer treatment. Our goal was to determine if ascorbate, in combination with other antioxidants, could kill cells in the SW620 hollow fibre in vitro solid tumour model at clinically achievable concentrations. Ascorbate anti-cancer efficacy, alone or in combination with lipoic acid, vitamin K3, phenyl ascorbate, or doxorubicin, was assessed using annexin V staining and standard survival assays. 2-day treatments with 10 mM ascorbate increased the percentage of apoptotic cells in SW620 hollow fibre tumours. Lipoic acid synergistically enhanced ascorbate cytotoxicity, reducing the 2-day LC(50)in hollow fibre tumours from 34 mM to 4 mM. Lipoic acid, unlike ascorbate, was equally effective against proliferating and non-proliferating cells. Ascorbate levels in human blood plasma were measured during and after intravenous ascorbate infusions. Infusions of 60 g produced peak plasma concentrations exceeding 20 mM with an area under the curve (24 h) of 76 mM h. Thus, tumoricidal concentrations may be achievable in vivo. Ascorbate efficacy was enhanced in an additive fashion by phenyl ascorbate or vitamin K3. The effect of ascorbate on doxorubicin efficacy was concentration dependent; low doses were protective while high doses increased cell killing.

Topics: Antioxidants; Apoptosis; Ascorbic Acid; Carcinoma; Colonic Neoplasms; Dose-Response Relationship, Drug; Doxorubicin; Drug Interactions; Humans; Necrosis; Thioctic Acid; Tumor Cells, Cultured

Scanning and transmission electron microscopy (SEM and TEM) were employed to characterize the cytotoxic effects of vitamin C (VC), Vitamin K3 (VK3) or a VC:VK3 combination on a human bladder carcinoma cell line (T24) following vitamin treatment. T24 cells exposed to VC alone showed membrane defects. VK3-treated cells show greater damage than VC treated cells because they exhibit membrane defects, cytoskeletal damage, excision of cytoplasm, and a substantial decrease in the number of viable cells. VC: VK3 treatment exacerbates the damages, especially intranuclear and nucleolar and induces an extreme reduction of cell size by cytoplasmic self-excision. Conversely, the nuclear envelope remains intact and the rough endoplasmic reticulum (RER) maintains its integrity until karyorrhexis occurs through a new phenomenon of cell death that we have named "autoschizis". From our morphological studies and previous biochemical reports on the topic, we are able to propose that this autoschizic cell death found is induced by oxidative stress.

Topics: Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Carcinoma; Cell Death; Drug Therapy, Combination; Humans; Microscopy, Electron; Oxidative Stress; Treatment Outcome; Tumor Cells, Cultured; Urinary Bladder Neoplasms; Vitamin K 3

Overexpression of ornithine decarboxylase (ODC) has been shown to be characteristic of tumor development and progression in humans and experimental animals. Therefore, we have examined the effects of 1, 3-diaminopropane dihydrochloride (DAP), a potent inhibitor of ODC, on rat two-stage urinary bladder carcinogenesis initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). In experiment 1 (36 weeks), 6-week-old F344 male rats were administered 0.05% BBN in drinking water for 4 weeks and then divided into four groups. Animals of groups 1 and 2 received basal diet and drinking water supplemented with or without DAP (2 g/l). Groups 3 and 4 were given diet containing 5% sodium L-ascorbate (NaAsA), a typical urinary bladder tumor promoter, and drinking water with or without DAP. Administration of DAP to group 1 significantly reduced tumor size, multiplicity and incidence, particularly of papillomas, when compared with group 2 values. DAP together with NaAsA (group 3) also decreased tumor size relative to the group 4 case. To determine the effects of DAP on the early stages of bladder carcinogenesis and its mechanisms, a similar protocol was conducted (experiment 2) with death after 20 weeks. DAP treatment caused complete inhibition (0% incidence) of papillary and/or nodular hyperplasia in group 1 but was without influence in group 3, as compared with the respective controls. Moreover, the ODC activity, bromodeoxyuridine labeling indices and mRNA expression levels of cyclin D1 in the urinary bladder mucosa, determined by northern blotting, were markedly lower in group 1 than in group 2, but values were comparable for both groups administered NaAsA. Assessment of mRNA expression levels of the angiogenic vascular endothelial growth factor suggested no involvement in the inhibitory effects of DAP on urinary bladder carcinogenesis. The results indicate that inhibition of ODC could reduce urinary bladder carcinogenesis in rats, particularly in the early stages, through antiproliferative mechanisms.

Topics: Acetyltransferases; Animals; Anticarcinogenic Agents; Apoptosis; Ascorbic Acid; Butylhydroxybutylnitrosamine; Carcinogens; Carcinoma; Cocarcinogenesis; Cyclin D1; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinases; Diamines; Endothelial Growth Factors; Hydrogen-Ion Concentration; Hyperplasia; Lymphokines; Male; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors; Papilloma; Polyamines; Proto-Oncogene Proteins; Rats; Rats, Inbred F344; RNA, Messenger; Urinary Bladder; Urinary Bladder Neoplasms; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

In our two-stage model of rat urinary bladder carcinogenesis employing N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) as the initiator, sodium L-ascorbate (Na-AsA) exhibits dose-dependent promotion. In the present study, in order to assess the possible reversibility of the promoting effects, we investigated how different administration periods of Na-AsA influence its promoting activity. In experiment 1, rats were treated with 5% Na-AsA for different administration periods with or without withdrawal and injected with 5-bromo-2'-deoxyuridine (BrdU) to allow determination of the cell proliferation status. Replicative DNA synthesis in the urinary bladder epithelium was shown to return to normal after removal of the promoting stimulus. In experiment 2, rats were initially given BBN for 4 weeks and subsequently received 16 weeks of Na-AsA, alternating with basal diet, at intervals of 4, 8 or 16 weeks, within a total 32-week period. The longer the continuous exposure to Na-AsA, the greater the yield of papillomas and carcinomas in the urinary bladder. In experiment 3, Na-AsA was given for 4 or 8 weeks after BBN initiation and the animals were killed at weeks 8 and 12. Both promotion of lesion development and increase of DNA synthesis in the urinary bladder epithelium were dependent on the length of exposure to Na-AsA and the total period of exposure. The results indicate that the promoting effects of Na-AsA in urinary bladder carcinogenesis are reversible to a certain extent after its withdrawal, and the existence of a cumulative exposure time threshold seems likely.

Topics: Animals; Ascorbic Acid; Bromodeoxyuridine; Butylhydroxybutylnitrosamine; Carcinogens; Carcinoma; Drug Administration Schedule; Hyperplasia; Male; Papilloma; Rats; Rats, Inbred F344; Time Factors; Urinary Bladder; Urinary Bladder Neoplasms

Dimethylarsinic acid (DMA), a main metabolite of arsenicals which are carcinogenic in man, exerts tumor-promoting activity on rat urinary bladder carcinogenesis initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Sodium L-ascorbate (Na-AsA) is also a strong tumor promoter in this animal model. In this study, we used (LewisxF344)F, rats to compare molecular alterations in urinary bladder tumors caused by BBN followed by DMA or Na-AsA. Male, 6-week-old rats were given 0.05% BBN in their drinking water for 4 weeks, and then the rats in group 1 were maintained with no further treatment for 40 weeks. The animals of groups 2 and 3 were administered 0.01% DMA in their drinking water (group 2) or 5% Na-AsA in the powder diet (group 3) after the BBN treatment. Group 4 rats were given 0.05% BBN continuously for 36 weeks. At weeks 12, 20, 36 and 44, subgroups of rats were killed. Histopathological examination revealed promoting activity for DMA and, to a greater extent, Na-AsA on urinary bladder carcinogenesis. Loss of heterozygosity (LOH), detected with the polymerase chain reaction using 36 microsatellite markers, was found to be present in 2 of 9 (22%) urinary bladder tumors after treatment with DMA and 3 of 22 (14%) induced by continuous administration with BBN. No LOH was, however, detected in urinary bladder tumors after treatment with Na-AsA. The results thus suggest that the mechanisms of action of these two promoters, DMA and Na-AsA, may differ in rat urinary bladder carcinogenesis.

Topics: Animals; Ascorbic Acid; Butylhydroxybutylnitrosamine; Cacodylic Acid; Carcinogenicity Tests; Carcinoma; Hyperplasia; Loss of Heterozygosity; Male; Microsatellite Repeats; Papilloma; Polymerase Chain Reaction; Rats; Rats, Inbred F344; Rats, Inbred Lew; Urinary Bladder; Urinary Bladder Neoplasms

The aim of the present study was to elucidate the influence of social, dietary and environmental factors on the incidence of malignant epithelial tumours in the upper digestive tract and on the prognosis of patients with these cancers.. A population-based case-control study was carried out, and the patients in the study were included in a survival analysis.. The study was carried out at the Department of Otorhinolaryngology at Ullevål University Hospital, Oslo, Norway.. In the case-control study, 84 patients and 89 controls were included. Only the patients were included in the survival analysis.. Smoking showed the highest odds ratio (OR) for morbidity (OR = 29). The patients had in general a lower social status, and a higher alcohol intake (OR = 6.6). For both beta-carotene and vitamin C, the ORs decreased with increasing intake (OR = 0.2 and 0.3, respectively). Increased ORs were associated with low values for haemoglobin, iron, TIBC, folic acid, magnesium and especially for albumin (OR = 14), and with high values for ferritin, vitamin B12 and thiocyanate (a marker for smoking). Stage of the disease was an important prognostic factor. The relative risk (RR) of dying for disseminated vs localised tumours being 3.2. A poorer prognosis was linked to higher age, to smoking vs no smoking (RR = 2.3), and to lower levels of haemoglobin, albumin, magnesium and thiocyanate.. Strong beer, liquor, consumption of milk and table fat, low social status and smoking seemed to have a negative impact on both disease and survival. Fruit and vegetables might, however, reduce the risk. Whereas low serum albumin, iron and magnesium indicated a high OR for cancer, vitamin C and beta-carotene had the opposite implication. No significant implications on survival could be detected in blood chemistry beyond the stage of disease.

Topics: Adult; Aged; Alcohol Drinking; Ascorbic Acid; beta Carotene; Carcinoma; Case-Control Studies; Diet; Dietary Fats; Digestive System Neoplasms; Female; Humans; Male; Middle Aged; Norway; Prognosis; Smoking; Social Class; Survival Analysis

Topics: Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Carcinoma; Cell Death; Humans; Microscopy, Electron; Microscopy, Electron, Scanning; Tumor Cells, Cultured; Urinary Bladder Neoplasms; Vitamin K 1

Topics: Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Carcinoma; Cell Death; Drug Synergism; Humans; Microscopy, Electron; Microscopy, Electron, Scanning; Time Factors; Tumor Cells, Cultured; Urinary Bladder Neoplasms; Vitamin K 1

Although many epidemiological studies indicate protective effect of vitamin C against a variety of human malignancies its mechanism(s) of action is questionable. The presented results show that the part of its effect may be accomplished by mononuclear cells, as necessary participants in body defence. Namely, in a long-term in vitro assay we tested vitamin C influence on random migration ability of malignant pleural effusion mononuclears (PEM) obtained from breast cancer patients. Vitamin C in a dose- (50-500 micrograms) and time-dependent (4-44 h) manner inhibited PEM motility, suggesting that immobilization of cells in situ may contribute to its beneficial effect in human cancers.

Topics: Ascorbic Acid; Breast Neoplasms; Carcinoma; Cell Migration Inhibition; Cell Movement; Female; Humans; Leukocytes, Mononuclear; Pleural Effusion, Malignant; Pleural Neoplasms

The study was designed to investigate whether sodium bicarbonate (NaHCO3) and/or L-ascorbic acid (AsA) promote urinary bladder carcinogenesis in male ODS/Shi-od/od (ODS) rats, which, unlike male F344 rats, are resistant to sodium L-ascorbate (Na-AsA)-promoting effects. Whereas F344 rats can synthesize AsA and alpha 2 mu-globulin (A2 mu-G), only A2 mu-G in produced in ODS rats. The two strains were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 2 wk and then were fed basal CA-1 diet supplemented with 3% NaHCO3 plus 5% AsA (NaHCO3 + AsA), 3% NaHCO3, 5% AsA, or no chemicals for 32 wk. ODS rats given BBN-NaHCO3 or BBN-(NaHCO3 + AsA) had only a few small carcinomas in the urinary bladder, like those receiving BBN alone or BBN-AsA. In contrast, F344 rats administered BBN-NaHCO3 or BBN-(NaHCO3 + AsA) had many more, larger, carcinoma than animals of the same strain given BBN alone or BBN-AsA. AsA alone did not have any effect in either strain. Administration of NaHCO3 alone or NaHCO3 + AsA was associated with significant elevation of urinary pH and Na+ concentration to the same extent in both strains but, again, AsA alone was without effect. NaHCO3 + AsA and AsA alone increased the urinary concentration of total ascorbic acid in both strains but the observed levels wer lower in ODS rats. The results indicate that ODS rats are resistant to the modifying effects of NaHCO3 and/or AsA on two-stage urinary bladder carcinogenesis, and thus that the susceptibility to the promotional activity of sodium-salt-type compounds may be regulated by factors other than A2 mu-G-synthesizing ability and urinary levels of pH, Na+ and total ascorbic acid.

Topics: alpha-Macroglobulins; Animals; Ascorbic Acid; Body Weight; Butylhydroxybutylnitrosamine; Carcinogens; Carcinoma; Cocarcinogenesis; Drug Combinations; Eating; Hydrogen-Ion Concentration; Male; Rats; Rats, Inbred F344; Rats, Mutant Strains; Sodium; Sodium Bicarbonate; Urinalysis; Urinary Bladder Neoplasms

Vitamins C, K3 (VC, VK3) and a VC/VK3 combination with a VC:VK3 ratio of 100:1 were assayed for their antitumour activity against two human prostatic carcinoma cell lines. Co-administration of the vitamins enhanced the antitumour activity 5- to 20-fold even with a 1 h exposure time. While exogenous catalase destroyed the antitumour activity, hydrogen peroxide-induced lipid peroxidation was negligible. Analysis of cellular ATP and thiol levels as well as DNA and protein synthesis revealed: a transient increase in ATP production, a decrease in DNA synthesis, an increase in protein synthesis and a decrease in thiol levels. These results suggested that the increased cytotoxicity of the vitamin combination was due to redox cycling and increased oxidative stress.

Topics: Adenosine Triphosphate; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Carcinoma; Catalase; DNA, Neoplasm; Humans; Hydrogen Peroxide; Lipid Peroxidation; Male; Neoplasm Proteins; Prostatic Neoplasms; Sulfhydryl Compounds; Tumor Cells, Cultured; Vitamin K

A MTT/formazan assay was used to evaluate the antitumor activity of vitamin C (Vit C), vitamin K3 (Vit K3), or vitamin C:vitamin K3 combinations against a human prostatic carcinoma cell line (DU145). Both Vit C and Vit K3 alone exhibited antitumor activity, but only at elevated doses. When Vit C and Vit K3 were combined at a C:K3 ratio of 100:1 and administered to the carcinoma cells, the 50% cytotoxic concentrations (CD50) of the vitamins decreased 10- to 60-fold. Subsequently, the DU145 cells were examined with transmission and scanning electron microscopy (TEM and SEM) following a 1 hour treatment with Vit C, Vit K3, or Vit C/K3 combined at their 50% cytotoxic dose. Our morphological data suggest that vitamin treatment with individual vitamins affects the cytoskeleton, the mitochondria, and other membranous components of the cell. Treatment with the vitamin combination appears to potentiate the effects of the individual vitamin treatment. Specifically, there are abundant necrotic cells. The surviving cells display morphological defects characteristic of cell injury.

Topics: Antineoplastic Agents; Ascorbic Acid; Carcinoma; Cell Membrane; Coloring Agents; Cytoskeleton; Drug Synergism; Drug Therapy, Combination; Humans; Male; Microscopy, Electron; Microscopy, Electron, Scanning; Mitochondria; Prostatic Neoplasms; Tetrazolium Salts; Thiazoles; Tumor Cells, Cultured; Vitamin K

A single dose of 10 mg of 7,12-dimethylbenz[a]anthracene (DMBA), administered to rats through intragastric intubation, was sufficient to induce many biochemical and histopathological changes in their mammary tissue. Significant increases were observed in the activity levels of the enzymes acid ribonuclease, 5-nucleotidase, alkaline phosphatase, and beta-glucuronidase in mammary tissue homogenates of DMBA-treated rats after an experimental period of five months. Histopathological studies of the mammary tissue also revealed malignant epithelial tumors (cribriform carcinoma) induced among 85% of the treated rats, with an incidence of 4 tumors in 12 mammary glands. Nevertheless, administration of 30% soybean in the diet of rats or 5,000 ppm ascorbic acid in their drinking water in addition to DMBA revealed a significant chemoprotective effect against the carcinogenesis induced by DMBA alone. This chemoprotective effect was demonstrated by the normalization of the activity levels of the enzymes studied in mammary tissue homogenates, because most of the enzymes were maintained at near the levels in the control animals. The incidence and number of tumors were also decreased. Cribriform carcinoma was observed in 50% of the rats, and the incidence of the affected glands was 2 in 12 mammary glands among both groups. On the other hand, a less chemoprotective effect was observed due to Vicia faba administration.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Ascorbic Acid; Carcinoma; Dose-Response Relationship, Drug; Female; Glycine max; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Rats

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

The dose dependence of K2CO3 promotion of two-stage urinary bladder carcinogenesis and the amplifying effects of additional L-ascorbic acid (AsA) administration were investigated. Male F344 rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in their drinking water for 4 weeks and then fed basal diet containing K2CO3 at levels of 0, 1, 1.5, 2.2, and 3% with or without 5% AsA or 3% NaHCO3 supplementation from weeks 5 to 8 (4 weeks) and weeks 12 to 20 (9 weeks). During weeks 9 to 11 (3 weeks), the rats were fed 3% uracil in their diet. For controls, rats without N-butyl-N-(4-hydroxybutyl)nitrosamine treatment were given either 3% K2CO3, 5% AsA, or both plus the uracil treatment. The total observation period was 20 weeks. K2CO3 dose dependently increased the numbers of the putative preneoplastic lesion, papillary or nodular hyperplasia, and papillomas in rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine. AsA (5%), while itself exerting no promoting effect, amplified the enhancing influence of K2CO3 on the induction of papillary or nodular hyperplasia and papillomas. The dose-dependent elevation of urinary pH and K+ concentration was associated with K2CO3 treatment with or without AsA. Thus, increased urinary pH and K+ concentration appear to play important roles in K2CO3 promotion, and AsA amplifies this promotion.

Topics: Animals; Ascorbic Acid; Body Weight; Carbonates; Carcinoma; Drug Synergism; Hyperplasia; Male; Organ Size; Papilloma; Potassium; Rats; Rats, Inbred F344; Reference Values; Urinary Bladder; Urinary Bladder Neoplasms

Male F344 rats were fed 0.2% N-[4-(5-nitro-2-furyl)-2-thiazoly]formamide for 6 weeks and then fed 3% or 5% sodium saccharin, 5% sodium ascorbate, 3.12% calcium saccharin, 1.34% sodium chloride, 5.2% calcium saccharin plus 1.34% sodium chloride, or basal diet alone for 72 weeks. Protein and DNA were extracted from 89 bladder tumors [87 transitional cell carcinomas (TCC), 1 papilloma, and 1 sarcoma] from 86 rats p21 expression was examined by Western blotting using a monoclonal antibody against p21 (NCC-RAS-004). H-ras mutations in exons 1 and 2 were examined by direct sequencing of DNA amplified by polymerase chain reaction. Sequencing results demonstrated mutations at codon 61 (CAA to CGA in 15 TCCs; CAA to CTA in 2 TCCs), at codon 12 (GGA to TGG in 1 TCC), and at codon 13 (GGC to GTC in 3 TCCs). Mutations at codon 61 were confirmed by faster mobility of the p21 band in Western blots. The level of p21 expression varied among samples, but many TCCs appeared to express more p21 than controls. The overall incidence of H-ras mutations was 24.4% (21 of 86 rats). The type of chemical used for the promoting phase had essentially no effect on H-ras mutation, suggesting that the effects observed were related to FANFT administration. The frequency of H-ras mutation in each group was negatively related to the incidence of carcinoma (r = -0.85; P less than 0.01). Two groups of tumors (with or without the mutated ras gene) were compared for tumor size (reflected by the bladder weight), histological grading, and the presence of invasion. The size of tumors with mutated ras was significantly smaller than those without mutated ras. There was no difference in the histological grading between the two groups. Although not statistically significant, histological invasion was more frequently observed in tumors with mutated ras (14.3%) than in tumors without mutation (3.1%).

Topics: Animals; Ascorbic Acid; Base Sequence; Blotting, Western; Carcinogens; Carcinoma; Carcinoma, Transitional Cell; DNA, Neoplasm; FANFT; Genes, ras; Male; Mutation; Proto-Oncogene Proteins p21(ras); Rats; Rats, Inbred F344; Saccharin; Urinary Bladder Neoplasms

Potential second-stage modifying effects of 8 antioxidants on lung tumorigenesis initiated by N-bis(2-hydroxypropyl)nitrosamine (DHPN) were examined in male F344 rats. After an initial 2-week treatment with DHPN (0.1% in drinking water), rats were administered one of the antioxidants supplemented in the diet for 30 weeks. Although the incidences of lung adenomas were not affected, those of carcinomas were lowered by 2% butylated hydroxyanisole (BHA, 2 rats/20 rats), 1% butylated hydroxytoluene (BHT, 1/20), 0.8% ethoxyquin (EQ, 3/20) and 1% a-tocopherol (a-TP, 2/20) treatments as compared to the control level (9/20), while 5% sodium L-ascorbate (SA), 0.8% catechol (CC), 0.8% resorcinol (RN), and 0.8% hydroquinone (HQ) did not exert any significant effect on incidence. Quantitative analysis of adenomas and carcinomas (numbers and areas of lesions per unit area of lung section) revealed obvious inhibitory effects of SA, CC, and RN as well as BHA, BHT, EQ, and a-TP. Among the antioxidants, BHT exerted the strongest inhibitory activity. In contrast, DHPN-induced thyroid tumorigenesis was significantly enhanced by BHT (14/20) and EQ (20/20) treatments (control = 5/20). Thus the antioxidants showed opposite effects on lung and thyroid carcinogenesis in the rat.

Topics: Adenoma; Animals; Antioxidants; Ascorbic Acid; Body Weight; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Carcinoma; Catechols; Ethoxyquin; Hydroquinones; Kidney Neoplasms; Lung Neoplasms; Male; Nitrosamines; Organ Size; Rats; Rats, Inbred F344; Resorcinols; Thyroid Neoplasms; Urinary Bladder Neoplasms; Vitamin E

The influences of strain and diet on the promoting effects of sodium L-ascorbate (SA) on two-stage urinary bladder carcinogenesis was investigated in male F344 and Lewis rats. Two kinds of commercial basal diets, Oriental MF and Clea CA-1, were used. Rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in their drinking water for 4 weeks and then basal diet with 5% SA or without SA for 32 weeks. Treatment with SA increased the induction of neoplastic lesions of the urinary bladder in rats initiated by 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine. The promoting effect of SA for urinary bladder carcinogenesis was: F344 strain-Oriental MF diet greater than Lewis strain-Clea CA-1 diet greater than F344 strain-Clea CA-1 diet = Lewis stain-Oriental MF diet. In both strains or with both diets, SA-treatment increased the urinary pH and the concentrations of sodium ion and total ascorbic acid. These results demonstrate that strain and diet strongly influence susceptibility to the SA-promoting effects in rat urinary bladder carcinogenesis.

Topics: Animals; Ascorbic Acid; Butylhydroxybutylnitrosamine; Carcinoma; Cocarcinogenesis; Diet; Hydrogen-Ion Concentration; Rats; Rats, Inbred F344; Rats, Inbred Lew; Sodium; Urinary Bladder Neoplasms

The effects of antioxidants given in the post initiation phase of colon tumor development were investigated in male F344 rats treated with 1,2-dimethylhydrazine (DMH). Animals (20/group) were given s.c. injections of DMH at a dose of 20 mg/kg once a week for four consecutive weeks. One week after the last injection, rats were fed diet containing 5% sodium L-ascorbate (SA), 0.5% butylated hydroxyanisole (BHA), 0.8% ethoxyquin (EQ), 1.0% propyl gallate or 0.5% butylated hydroxytoluene (BHT) for 36 weeks. A control group was fed the basal diet not containing antioxidants. The experiment was terminated 40 weeks after the first injection of DMH and all intestinal tumors were confirmed histologically. SA significantly increased the incidence of adenomas and the number of tumors per rat of the colon (especially of the distal colon). Although EQ and BHT did not affect the number of rats with colon tumors, the number of tumors per rat occurring in the distal colon was significantly increased by EQ while being decreased by BHT. No modification of tumor development was observed with BHA or PG. Thus, modification of tumor development by SA, EQ and BHT was apparent, mainly in the distal colon.

Topics: 1,2-Dimethylhydrazine; Adenoma; Animals; Antioxidants; Ascorbic Acid; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Carcinoma; Colonic Neoplasms; Dimethylhydrazines; Ethoxyquin; Male; Propyl Gallate; Rats; Rats, Inbred F344

Topics: Adult; Ascorbic Acid; Binding, Competitive; Calcitonin; Carcinoma; Humans; Kidney Failure, Chronic; Radioimmunoassay; Thyroid Neoplasms; Urea

Topics: Adenocarcinoma; Adult; Aged; Ascorbic Acid; Carcinoma; Combined Modality Therapy; Female; Fluorouracil; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Metastasis; Postoperative Care; Stomach Neoplasms

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

The possible inhibitory effect of vitamin C (sodium ascorbate) on metastases from two transplantable murine tumors was studied. The first murine tumor, colon carcinoma CA-51, was subcutaneously transplanted into male Balb/c mice. Immediately after tumor implantation, the mice were given either 1.0% sodium ascorbate or tap water. Subcutaneous tumors were surgically removed from one half of the animals in each group when the tumors reached a size of 1.5 cm. Results indicated no differences in survival, in the number of mice with metastases, or in the size of metastases between treated and untreated groups. The second murine tumor, lymphosarcoma 6C3HED, was subcutaneously implanted into C3H male and female mice. Sodium ascorbate (1.0% or 3.0%) was administered as above, but surgery was not performed. Again, no significant differences in the number of mice with metastases were observed between treated and untreated groups, with the exception of brain and regional lymph node metastases (enhanced, in males, by ascorbate).

Topics: Animals; Ascorbic Acid; Carcinoma; Colonic Neoplasms; Female; Lymphoma, Non-Hodgkin; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Neoplasm Metastasis; Neoplasms, Experimental

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: 2-Naphthylamine; 3-Hydroxyanthranilic Acid; Animals; Ascorbic Acid; Carcinoma; Dogs; Humans; Smoking; Urinary Bladder Neoplasms

The authors report the results of studies on the content of ascorbic acid, pyruvic acid and the activity of malate dehydrogenase decarboxylizing (MDHD) in cell nuclei of uterine fibromyoma, glandular hyperplasia of the endometrium with epithelial proliferation, common ovarian cyst and solid cancer. It was shown that due to the glycolysis inhibited respiration an oxidated form of ascorbic acid is absent in every case, whereas the MDHD activity is not manifested. The amount of a reduced form of ascorbic and pyruvic acid in benign tumors is at the control level, but in malignant growth these indices are markedly increased.

Topics: Ascorbic Acid; Carcinoma; Cell Nucleus; Decarboxylation; Endometrial Hyperplasia; Female; Humans; Hydroxy Acids; Keto Acids; Leiomyoma; Malate Dehydrogenase; Ovarian Cysts; Ovarian Neoplasms; Pyruvates; Uterine 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: Administration, Oral; Ascorbic Acid; Breast Neoplasms; Carcinoma; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Evaluation; Drug Stability; Female; Fibrosarcoma; Humans; Injections, Intravenous; Neoplasms; Papilloma; Rectal Neoplasms; Stomach Neoplasms; Time Factors; Urinary Bladder Neoplasms

Topics: Adolescent; Aged; Ascorbic Acid; Carcinoma; Child; Child, Preschool; Humans; Leukemia, Lymphoid; Leukocytes; Lung Neoplasms; Male; Middle Aged; Neoplasms; Skin; Skin Neoplasms

Topics: Animals; Ascorbic Acid; Benzopyrenes; Carcinoma; Carcinoma, Ehrlich Tumor; Dipyridamole; Female; Glucose; Hyperbaric Oxygenation; Male; Methods; Mice; Neoplasms, Experimental; Rats; Sarcoma, Experimental; Sarcoma, Yoshida; Vitamin A; Vitamin B Complex

Topics: Adult; Aged; Alkaline Phosphatase; Amyloidosis; Ascorbic Acid; Carcinoma; Glycosaminoglycans; Histocytochemistry; Humans; Lymphatic Metastasis; Male; Methods; Microscopy, Electron; Middle Aged; Nucleic Acids; Thyroid Gland; Thyroid Neoplasms

Topics: Ascorbic Acid; Blood; Carcinoma; Catalase; Conductometry; Dialysis; Edetic Acid; Erythrocytes; Ethylmaleimide; Hemolysis; Hot Temperature; Humans; Kidney; Liver; Lung Neoplasms; Male; Neoplasms; Prostatic Neoplasms; Stomach Neoplasms; Tissue Extracts; Triazoles

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: Animals; Ascites; Ascorbic Acid; Carcinoma; In Vitro Techniques; Neoplasms, Experimental; Sarcoma, Experimental; Sarcoma, Yoshida; Vitamins

Topics: Ascorbic Acid; Carcinoma; Humans; Neoplasms; Vitamin A; Vitamins

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

Topics: Ascorbic Acid; Carcinoma; Female; Genitalia; Genitalia, Female; Humans; Neoplasms; Vitamin A; Vitamins

Topics: Ascorbic Acid; Carcinoma; Humans; Neoplasms; Vitamin A; Vitamins

Topics: Ascorbic Acid; Blood Pressure; Blood Pressure Determination; Carcinoma; Humans; Hypertension; Vitamins