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

Oral contraceptives are used among women worldwide, and radiation is being used increasingly for diagnosis or therapy, We have investigated the effect s of contraceptive steroids on the risk of mammary tumors initiated by radi ation. Virgin rats received whole-body irradiation with 2.6 Gy gamma-rays 1 month after the administration of low- or high-dose pellets of contracepti ve steroids, such as 17 alpha-ethinylestradiol (EE2) combined with 19-noret histerone (NET), The high-dose pellet was removed 1 month after irradiation , but administration of the low-dose pellet was continued for up to 1 gear. The incidence (33.3%) of mammary tumors initiated with radiation was not m odified by the long-term administration of the low-dose pellets. However, t he incidence (58.3%) was increased significantly by the irradiation during administration of the high-dose pellets, but no significant difference in t he proportion of adenocarcinoma and fibroadenoma was observed. Meanwhile, p arous rats were irradiated with 2.6 Gy gamma-rays at weaning, a period of g reater susceptibility to radiation, and then were implanted with the low-do se pellets 1 month later. The highest incidence (90%) of mammary tumors was detected in the parous rats. The proportion of adenocarcinomas in the paro us irradiated rats increased significantly on treatment with the low-dose p ellets. The results suggest that administration of the high-dose pellets of EE2-NET, but not of the low-dose pellets, enhances susceptibility to the i nitiation 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 i rradiated at weaning.