PROMOTING EFFECTS OF ETHINYL ESTRADIOL ON DEVELOPMENT OF RENAL PROLIFERATIVE LESIONS INDUCED BY N-NITROSOBIS (2-OXOPROPYL)AMINE IN FEMALE SYRIAN GOLDEN-HAMSTERS

The modulating effects of female sex hormones, ethinylestradiol and le vonorgestrel, on the development of renal proliferative lesions after initiation with N-nitrosobis(2-oxopropyl)amine (BOP) were investigated . Three groups of female Syrian golden hamsters, each comprising 30 an imals, were given four weekly s.c. injections of BOP (10 mg/kg body we ight) and then fed diet containing 1 ppm ethinylestradiol (group 1: BO P/EE), diet containing 10 ppm levonorgestrel (group 2) or basal diet ( group 3) for the next 27 weeks. As hormone controls, two groups of 20 female hamsters each received diet containing 1 ppm ethynylestradiol ( group 4) and 10 ppm levonorgestrel (group 5) from week 3 for 27 weeks without the prior initiation treatment. The severity of diffuse anisok arya, characterized by varied nuclear size and the incidence of dyspla sias of the proximal tubular epithelia induced by BOP, were significan tly increased in the BOP/EE group, indicating the promoting effects of the hormone. In the renal dysplastic lesions (small-cluster, cystic, clear-cell and acidophilic cell types), adenomas and nephroblastomas, increases in the numbers of argyrophilic proteins associated with nucl eolar organizer regions (NOR) in the nucleus, suggesting a high prolif erative activity, were seen in dysplasia of acidophilic cell types and adenomas. In addition, the number of bizarre NOR per nucleus was sign ificantly higher in adenomas than in dysplasias and highest in nephrob lastomas. This morphological change in NOR should therefore be a usefu l parameter for the diagnosis of malignancy of renal tumors.