Comparative effect of chlormadinone acetate and diethylstilbestrol as promoters in mammary tumorigenesis of rats irradiated with gamma-rays during lactation.

The purpose of this study was to determine the promotional role of estrogen and progestin in the development of radiation-induced mammary tumors. To eliminate the effects of endogenous ovarian hormones on tumor promotion, all rats were ovariectomized immediately after the initiation by irradiation with 2.6 Gy gamma-rays at day 21 of lactation, and were divided into 3 groups. For the control experiment, rats were implanted with a cholesterol pellet 1 month after the irradiation. Only one rat developed a fibroadenoma (4.3% mammary tumor incidence) during the 1 year period of the implantation. In the other two groups, chlormadinone acetate (CMA) to increase progestin level or diethylstilbestrol (DES) to increase estrogenic activity were administered, respectively, as tumor promoters for 1 year. Treatment with CMA did not significantly increase the incidence of mammary tumors as compared with the controls. However, administration of DES resulted in a significantly higher mammary tumor incidence (79.3%) than control treatment. Compared with cholesterol administration, DES treatment caused an increase in prolactin concentration in serum (5-fold), and reduction of estradiol-17beta concentration (22% of control). These results suggest that DES ia a potent effective promoter for tumorigenesis of radiation-initiated mammary cells, but CMA is not. DES may act directly on the irradiated mammary cells by binding to ER, and indirectly by stimulating prolactin secretion from the pituitary glands.