sodium-nitrite and Urinary-Bladder-Neoplasms

Nitrite has been implicated in carcinogenesis, especially under acidic conditions such as in the stomach or in urine, where it forms nitrosating species that can react with secondary amines to form nitrosamines. Recent studies have shown that nitrite and acid form a variety of other nitrogen oxides in vivo including nitric oxide-a compound with documented antitumor activity. Here we tested the effects of nitrite on bladder tumor cells incubated in mildly acidified urine. Nitrite (50 microM) inhibited thymidine incorporation in human T24 bladder cancer cells. This inhibition required slight acidification (pH 5.5-6), and no effect of nitrite could be observed at pH 7. Nitrite effects were further augmented in the presence of ascorbic acid, whereas ascorbic acid alone had no effect. The effects were paralleled by formation of nitric oxide gas. We here demonstrate an inhibitory effect of nitrite on cancer cell replication at concentrations and acidity commonly found in urine and gastric juice. The inhibitory effect is likely caused by nitric oxide and possibly other reactive nitrogen oxides formed from acidified nitrite.

Topics: Antineoplastic Agents; Ascorbic Acid; Cell Line, Tumor; DNA Replication; Drug Synergism; Humans; Hydrogen-Ion Concentration; Luminescent Measurements; Nitric Oxide; Nitrites; Sodium Nitrite; Thymidine; Urinary Bladder Neoplasms; Urine

Experimental data connected with prophylaxis of vesical cancer are reviewed. The following prophylactic measures are discussed: influence on metabolism of carcinogens and inactivation of metabolites; forced clearance of carcinogenic metabolites; carcinogenesis promoters arrest. Specific inhibition of beta-glucuronidase in urine and forced diuresis appeared to be extremely effective.

Topics: Animals; Chlorthalidone; Diuresis; Furosemide; Glucuronidase; Rats; Sodium Nitrite; Sodium Selenite; Urinary Bladder Neoplasms

The potential carcinogenic effect of nitrosamine precursors, DBA (dibutylamine) and nitrite, was clearly demonstrated pathologically in the liver and bladder of male Swiss albino mice. Benign tumours were induced in the bladder with an incidence of 40%, and hepatomas were detected in the liver in 27% of the cases. The protective effect of soybean and ascorbic acid, added separately to the diet or to the drinking water respectively, was demonstrated by a marked reduction in dysplastic features and absence of tumour in both the liver and the urinary bladder.

Topics: Animals; Ascorbic Acid; Butylamines; Glycine max; Liver; Liver Neoplasms, Experimental; Male; Mice; Mice, Inbred Strains; Nitrites; Sodium Nitrite; Urinary Bladder; Urinary Bladder Neoplasms

Using ascorbic acid as a model, this paper proposes that the concept of the RDA should be broadened to take into account the effects of ubiquitous pollutants on human health, a factor not specifically incorporated in RDA derivations. It is now widely accepted that ascorbic acid nutritional status markedly affects the toxicity and/or carcinogenicity of greater than 50 pollutants, many of which are ubiquitous in the air, water, and food environments. At the present time, the data do not warrant changing the ascorbic acid RDA in light of the knowledge of pollutant interactions.

Topics: Air Pollutants, Occupational; Animals; Ascorbic Acid; Carcinogens, Environmental; Diet; Environmental Health; Environmental Pollutants; Female; Guinea Pigs; Humans; Male; Mice; Models, Theoretical; Nitrosamines; Nutritional Physiological Phenomena; Nutritional Requirements; Occupational Diseases; Occupational Health Services; Rats; Smoking; Sodium Nitrite; Urinary Bladder Neoplasms

A review of long term animal studies of saccharin and sodium nitrite was undertaken to assess the effect of variability of selected protocol elements on the results obtained. These elements were divided into 4 general categories: design, including selection of test animals, basal diet, dosage form and doses of test substance, route of administration, and duration of exposure; observations, including gross observations during life and at necropsy, clinical tests, and histopathology; performance, including conduct of the test and animal husbandry; and analytical procedures, including chemical and statistical analyses. Because many of the protocol elements are not fully discussed in study reports, it was often impossible to determine what actually had been done. The review of various saccharin studies suggests that bladder tumors resulted following in utero exposure. In utero exposure with sodium nitrite did not appear to cause reticuloendothelial changes. The numerous variations in protocol elements in the nitrite studies precluded identification of a prime element responsible for the variation in reticuloendothelial changes observed. It can be concluded from this review that achievement of reproducibility in long term studies requires minimal variation of protocol elements for the new study.

Topics: Animals; Drug Contamination; Female; Male; Mononuclear Phagocyte System; Nitrites; Rats; Research Design; Saccharin; Sodium Nitrite; Species Specificity; Urinary Bladder Neoplasms