RELATIONSHIP BETWEEN INDUCTION OF MAMMARY-TUMORS AND CHANGE OF TESTICULAR FUNCTIONS IN MALE-RATS FOLLOWING GAMMA-RAY IRRADIATION AND OR DIETHYLSTILBESTROL/

Male Wistar-MS (W/MS), Fisher-344 (F-344) and Sprague-Dawley (SD) rats were divided into four groups including a control group implanted wit h a cholesterol pellet. Rats in the three experimental groups were tre ated with gamma-ray irradiation (260 cGy) alone, diethylstilbestrol (D ES) pellet implantation alone or both irradiation and DES, and all rat s were observed for detection of mammary tumors for 1 year. Morphologi cally, well-developed mammary glands were observed in the SD rats at a ges corresponding to the time of irradiation. But, the mammary glands in the W/MS and F-344 rats showed a lower degree of differentiation th an those in the SD rats. No mammary tumor developed spontaneously in t he W/MS and F-344 strains of rats during the experimental period. The rats administered both DES and irradiation showed significantly increa sed incidence of mammary tumors compared with the control, the inciden ce being 80.9% in the SD rats, 35.0% in the W/MS rats, and 9.4% in the F-344 rats, respectively. The incidence of tumor in the SD rats treat ed with irradiation alone and with DES alone was 9.5% and 14.3%, respe ctively, but no tumor development was observed in the F-344 rats treat ed with either irradiation alone or DES alone or in the W/MS rats trea ted with DES alone. The magnitude of the decrease of testicular weight in the SD rats implanted with DES after irradiation (to 70% of the co ntrol weight) was slightly less marked than that in either the W/MS (3 5%) or F-344 (16%) rats. The testicular atrophy showed a correlation w ith the accessory sex organ weight at the end of the experiment, serum testosterone concentration, and incidence of mammary tumors. Followin g administration of DES pellets after the irradiation, the activity of Delta(5)-3 beta- and of 17 beta-hydroxysteroid dehydrogenase in the t estes showed the order F-344 < W/MS = SD and F-344 = W/MS < SD, respec tively. Compared with the control, the irradiated F-344 rats implanted with DES pellets showed hypertrophied pituitary glands (10.7-fold, P < 0.01) as well as increased serum prolactin concentration (21.4-fold P < 0.01). Of the three strains treated with both irradiation and DES, the F-344 rats showed the highest concentration of serum prolactin bu t the lowest incidence of mammary tumors. Our results suggest that W/M S, F-344 and SD male rats have differing susceptibilities for the indu ction of mammary tumor following irradiation. We discuss the relations hip between testicular and pituitary functions and male mammary tumori genesis.