Radiation-induced mammary tumors in virgin and parous rats administered contraceptive steroids, 17alpha-ethinylestradiol and norethisterone

Oral contraceptives are used among women worldwide, and radiation is being used increasingly for diagnosis or therapy. We have investigated the effects of contraceptive steroids on the risk of mammary tumors initiated by radiation. Virgin rats received whole-body irradiation with 2.6 Gy gamma-rays 1 month after the administration of low- or high-dose pellets of contraceptive steroids, such as 17alpha-ethinylestradiol (EE(2)) combined with 19-norethisterone (NET). The high-dose pellet was removed 1 month after irradiation, but administration of the low-dose pellet was continued for up to 1 year. The incidence (33.3%) of mammary tumors initiated with radiation was not modified by the long-term administration of the low-dose pellets. However, the incidence (58. 3%) was increased significantly by the irradiation during administration of the high-dose pellets, but no significant difference in the proportion of adenocarcinoma and fibroadenoma was observed. Meanwhile, parous rats were irradiated with 2.6 Gy gamma-rays at weaning, a period of greater susceptibility to radiation, and then were implanted with the low-dose pellets 1 month later. The highest incidence (90%) of mammary tumors was detected in the parous rats. The proportion of adenocarcinomas in the parous irradiated rats increased significantly on treatment with the low-dose pellets. The results suggest that administration of the high-dose pellets of EE(2)-NET, but not of the low-dose pellets, enhances susceptibility to the initiation by gamma-rays of mammary tumors in virgin rats, and that the low-dose pellets act as a tumor promoter in the mammary glands of parous rats irradiated at weaning.