Influence of thiouracil on carcinoma induced by 2-acetaminofluorene.

Bielschowsky (2) reported the occurrence of carcinoma in the rat's thyroid gland made hyperplastic by administration of allyl thiourea when the carcinogen, 2-acetaminofluorene (AAF) was administered simultaneously. Applying a similar principle, we investigated the effects of administration of this carcinogen to rats in which hyperplasia of target organs was produced by injection of male and female sex hormones. No evidence of malignancy was observed in these organs under these circumstances, but it was found that simultaneous administration of sex hormones and AAF enhanced the development of carcinoma of the liver (4). At the same time, experiments were conducted designed to repeat the work of Bielschowsky, with minor variations. His observation regarding the development of thyroid malignancy was confirmed. It was noted also that the liver of rats receiving thiouracil was protected against the carcinogenic effect of AAF. The present communication reports (a) studies of the protective action of thiouracil against the hepatic lesions caused by AAF and (b) the effects on the thyroid gland of simultaneous administration of AAF and thiouracil. Inasmuch as thiouracil was found to protect the liver against carcinoma induced by AAF, and sex hormones enhanced the development of liver cancer, study of the protective action of thiouracil was extended to animals receiving AAF and sex hormones simultaneously. The effect of thiouracil on the development of liver cancer by p-dimethylaminoazobenzene was also investigated. In an attempt to study the mechanism by which thiouracil exerts its protective action, the effect of methionine was investigated, inasmuch as it has been suggested that thiouracil protects against dietary cirrhosis by lowering the requirement for methionine (6). The possible role of hypothyroidism in this protective mechanism was studied in experiments on thyroidectomized rats and on rats receiving thiouracil and thyroxin simultaneously.