Carcinogenic effects of niridazole in rats.
Niridazole was administered in the diet to rats at levels of 0.1, 0.05 and 0.025%. The drug induced adenomas and adenocarcinomas of the kidneys and forestomach papillomas.
Biomedical subjects
Publications and source records attributed to D B Clayson.
Niridazole was administered in the diet to rats at levels of 0.1, 0.05 and 0.025%. The drug induced adenomas and adenocarcinomas of the kidneys and forestomach papillomas.
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The carcinogenicity of 1-(5-nitro-2-thiazolyl)-2-imidazolidinone (niridazole), a widely used schistosomicide, was examined in Swiss mice and Syrian golden hamsters. Schistosoma mansoni infection was evaluated as a cofactor. High incidences of drug-related neoplasms of the forestomach, lungs, mammary glands, urinary tract, and ovaries were found in mice, and tumors of the forestomach and urinary tract were found in hamsters. Infection with schistosomes had no apparent influence on tumor incidence. The results indicated a need for reevaluation of the possible carcinogenicity of this drug in man and suggested that care should be taken during its clinical use.
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The morphologic effects and the retention and distribution times of single and multiple intratracheal instillations in Syrian hamsters of 7H-dibenzo[c,g]carbazole (DBC) and benzo[a]pyrene (BP) were compared. A single instillation of DBC induced slight changes in the hamster respiratory tract; however, five treatments caused tracheobronchial epithelial proliferation, cell hyperplasia, and occasionally, squamous metaplasia. The particle size of both carcinogens was approximately the same. BP in saline remained longer in the lungs than did DBC in saline. The shortest retention time was recorded when DBC was administered in aqueous solution, whereas multiple doses of DBC in aqueous solution did not markedly affect retention time. DBC passed from the lungs to the intestinal tract and was mainly excreted in the feces.
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Animal experiments to test for the possible carcinogenic activity of chemicals provide the best and only deeply researched method for the detection or environmental carcinogens for man. The fact that most known human carcinogens give tumors in animals encourages the belief that these tests have validity. However, there are significant differences in the numbers of the exposed populations of men and animals, in the part of the lifespan during which each is exposed, in the metabolic activation of the carcinogens, and in the longevity of men and experimental rodents. For regulatory purposes, we must assume that the results of bioassay in rodents will closely parallel tumor induction in man, although we cannot be sure of this. In some cases, such as rodent bladder tumors associated with bladder stone, or subcutaneous sarcomas arising locally to massive injection of food dyes, there may be reason to reject an association. It is only by continued research into the way in which both man and laboratory animals react to carcinogens that we may hope to refine our methodologies and obtain an accurate, well-defined net to trap potential environmental carcinogens without depriving the community of chemicals, through false associations or false positive results that may be of great value, sociiologically or economically.
Swiss mice received chronic treatment with the schistosomacide, niridazole, at 3 dose levels. Tumors were found in several organs, including stomach, lung, manary gland, ovary and bladder. Niridazole is, without doubt, carcinogenic to mice.
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Restriction of the total diet or the number of calories fed to rats and mice inhibits the formation of tumors in several tissues. Unless animals are fed equivalent levels of food, or attain equivalent body weights, it is difficult to assess the significance of the effect of other nutritional modifications on carcinogenesis. The effects of altering the levels of protein or fat are much less than those seen with dietary restriction. Feeding a protein-free diet is tolerated for a limited period and can alter the metabolism of carcinogens. It may thus affect the tumor incidence induced by one-shot carcinogens. Vitamins have specific effects on the activity of certain carcinogens, the fullest information being available for vitamin A, which has been shown to inhibit or enhance carcinogenesis, and vitamin C, which by reducing sodium nitrite, prevents nitrosation of secondary and tertiary amines occurring in acidic conditions of the stomach. Inorganic substances, such as iodine (thyroid) and copper (liver), may affect the tumor incidence in specific tissues. The metabolic activation of carcinogens is modified by enzyme induction and the administration of antioxidants. The relevance of these results to the induction of cancer in humans is briefly discussed.
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Groups of mice were exposed to various doses of ionizing radiation on one occasion. In two groups of animals the bladder carcinogens dibutylnitrosamine (DBNA) and 4-ethylsulphonyl-naphthalene-1-sulphonamide (ENS) were administered 48 hours after irradiation.Post mortem and histopathological examinations failed to show any significant lesion in the bladder of animals subjected to radiation per se. Furthermore, radiation did not influence the latent period or incidence of bladder tumours induced by DBNA and ENS. However, radiation shortened the latent period of mammary tumours and, in some groups, increased the incidence of such lesions. When radiation was combined with the chemical carcinogens there was a marked reduction in the incidence of mammary tumours.
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