Testing the antifertility drug enovid for carcinogenesis in five strains of mice.

In testing for any carcinogenic effect of certain hormones the choice of test strain or strains is extremely important. By selecting several inbred strains one obtains maximum genetic variability offering a greater chance of demonstrating carcinogenesis in regard to a number of organs or tissues. The five strains of mice chosen in this study (C3H/He, C3HfB/He, BALB/cHe, A/He, and C5BL/He) provided a test for effect of Enovid at sterilizing doses on occurrence of mammary tumors, ovarian tumors, hepatomas, cervical and vaginal tumors, adrenocortical adenomas, and hypophyseal tumors. Results indicated a slight inhibitor effect of Enovid on mammary tumors in C3H and adrenocortical adenomas in BALB/c and an even greater inhibiotry effect on hepatomas in C3HfB. No effect on ovarian tumors could be detected in the appropriate test provided by C3HfB. In BALB/c females epithelial lesions of the cervix and vagina were observed in both the treated females and the controls with a slight increase in the group treated with the highest dose. All were small lesions observed only in the histologic section. None had invaded beyond the wall of the vagina, and none had metastasized. None could be classified as a frank carcinoma. In the group treated with the highest dose of Enovid, the lesions showed slightly further progression than in the other groups. The most significant tumorigenic effect of the Enovid was the increase in hypophyseal tumors in the C5BL females at advanced age. Direct extrapolation from one strain to another, from one species to another, from mouse to humans, or from one human being to another would be risky because of genetic differences. Approaches to the problem in human beings are, however, suggested. Because of these observations in mice, it would be well, if possible, to collect hypophyses of women at postmortem who have previously been on birth control pills for some time and send these hypophyses to some central laboratory where they can be examined for any changes that might be attributed to the use of the antifertility drug.