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The effect of estradiol‐17‐phenylpropionate and estradiol benzoate on N‐nitrosomorpholine‐induced liver carcinogenesis in ovariectomized female rats

The influence of synthetic estrogens on the N‐nitrosomorpholine (NNM)‐induced liver carcinogenesis in ovariectomized young adult female rats was investigated and compared to rats which received only the carcinogen or estrogens. Estrogens when chronically administered after the cessation of carcinogen treatment increased the carcinogenic effect of NNM. In such conditioned animals the number of nodules per number of rats was 23/31, that of hepatocellular carcinomas 9/31, whereas in animals which received only the hepatocarcinogen the incidence of nodules and carcinomas in liver was respectively 11/31 and 3/31. Higher incidence of benign and malignant tumors in other organs was also observed in these animals. Rats which received a single dose of estrogens simultaneously with NNM developed slightly fewer tumors in liver and in other organs. Since under my experimental conditions the long‐term treatment with synthetic estrogens alone did not induce any focus, nodule or hepatocellular carcinoma in the liver, I suggest that the estrogens were acting rather as tumor promotors than true initiators of liver carcinogenesis.