Mammary Carcinogenesis by 3-Methylcholanthrene. II. Inhibitory Effect of Pregnancy and Lactation on Tumor Induction2

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Abstract
These experiments are compatible with our earlier postulation that in mammary carcinogenesis a two-stage mechanism exists: the initiating process induced by the action of carcinogen, and the promoting phase regulated by the hormones. Hormonal stimulation is ineffective in accelerating the appearance of a tumor in the absence of “latent” tumor cells. Our data further showed that hormones of pregnancy and lactation, rather than a direct local effect of lactation, are important factors in the inhibition of mammary carcinogenesis by 3-methylcholanthrene since the prevention of suckling in pregnant rats did not increase tumor incidence. Chemical determinations of the level of 3-methylcholanthrene in mammary tissues indicated that the clearance of the carcinogen from the mammary tissues was greatly accelerated in pregnant and lactating rats. It would therefore appear that two factors might be important: First, the accelerated rate of 3-methylcholanthrene metabolism in pregnant and lactating rats prevented concentration of the carcinogen in the target tissue, and, second, the abnormal functional state of the mammary gland produced by the excessive hormones elaborated during pregnancy. The data suggested that the critical requirements for the induction of mammary cancer by 3-methylcholanthrene are dependent upon (a) an adequate time for the initiating process, (b) the concentration and persistence of the carcinogen in the target tissue for its effect, and (c) the functional state of the mammary gland exposed to the carcinogen.