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( Roswell Park Memorial Institute, 666 Elm Street, Department of Health, State of New York, Buffalo, New York)
The current studies demonstrate the critical importance of ovarian hormones in the initiation and promotion of carcinogenesis of mammary glands in rats by polynuclear hydrocarbons. Removal of ovarian hormones from the rats immediately after the administration of the carcinogenic hydrocarbons either inhibited or profoundly reduced the incidence of mammary cancer. Excision of ovaries beyond 7 days after feeding of carcinogenic hydrocarbon, however, was unable to prevent or to reduce significantly the incidence of mammary cancer in these rats. Likewise, feeding of carcinogenic hydrocarbons to already castrated rats failed to induce any mammary cancer if the time between castration and feeding of carcinogen was prolonged. These experiments suggest that neoplastic transformation in the cells of the mammary glands in rats cannot take place in the absence of the participation of ovarian hormones, since subsequent supply of ovarian hormones from the functioning grafts failed to produce any mammary cancers.
The experiments also indicate that there may be a quantitative balance between the carcinogenic polynuclear hydrocarbon and the hormones which govern the induction of mammary cancer in rats. In a small number of rats, a potent carcinogen was capable of inducing cancer in the mammary glands in which the metabolic activity was decreasing after the removal of ovarian hormones, whereas a "less potent" carcinogen failed to do so under the same circumstances. In these animals receiving a less potent carcinogen, mammary cancer could be induced if optimal ovarian hormones are present.
Some of the rats receiving a toxic dose of DMBA (30 mg.) died of adrenal apoplexy. DMBA caused necrosis and hemorrhage mostly in the inner zones, especially the zona reticularis of the cortex, whereas zona glomerulosa and medulla were frequently spared.
An incidental finding in the present experiment was the observation of chloroleukemia in two out of 100 rats receiving a single dose of 30 mg. DMBA.
* This work was supported by Grant C-4632-C1 from the National Cancer Institute, Public Health Service.
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