乳癌起始過程における卵巣ホルモンの作用

抄録

In order to investigate the actions of ovarian hormones in initiating the induction of mammary cancer by 7,12-Dimethylbenz(a)anthracene,85 young adult female JCLSprague-Dawley rats were divided to 3 main experimental groups: non-operated control group, ovariectomized control group and the groups administered with exogeneous ovarian hormones immediately after the ovariectomy. Daily examinations on the vaginal smears of all experimental rats were done aroun 9.00am frcm the age of 45 days, when their vaginas opened already, to the time of autopsy. Ovariectomy was performed around the age of 48-50 days. In the 1st experiment, the ovariectomized, hormone-injected groups were received by daily subcutaneous injections of oily solution of Estradio1-17p (E)0.4μg, E 20 fig, Progesterone (P) 4 mg, E 0.4μg + P 4 mg, and E 20μg + P 4 mg, respectively, from the age of 52 days to 70 days. All ovariectomized rats of the 1st experiment were injected daily by E 0.4μg P 4 rug from the age of 71 days to the time of autopsy. In the 2nd experiment, the ovariectomized rats started to be treated every 6 days with the implantation of pellet of cholesterol, E 1μg, P 4 mg, and E 1μg P 4mg, respectively, on the age of 48 days, and they exchanged on the age of 72days and continued through the experiment to be implanted weekly by the pellet of E 1μg + P 4 mg. All experimental animals were injected intravenously by 3 nag of 7,12-DMBA twice around the age of 60 days, and they were sacrificed to observe the induction of mammary tumors 3 months after the 1st intravenous injection. On this carcinogenesis, a half month after the administration of carcinogen might be speculated to be the initiation stage, and the following process would be the growthpromotion stage. Biopsy on thesmammary tissue was performed on the time of carcinogenadministration and of sacrifice. Morphological appearances of the glands and tumors were observed histochemically and electron-microscopically.
The non-operated controls of both experiments showed a regular sex cycle throughout the experiment. All ovariectomized control and progesterone-treated rats did never reveal an estrous stage, but the estrogen-treated rats did a continious estrus. E and Pinjected rats showed no estrous stages, but E and P-implanted rats did estrous cycles of 6-7 days throughout the experiment. The vaginal smears and the autopsy findings might suggest that the E and P-implantation in the promotion stage did compensate more to ovariectomy than the E and P-injection. The morphologic findings on the mammary tissue were different from each other groups, reflecting the hormonal conditions of each groups. All induced mammary tumors revealed moderately anaplastic pictures of adenocarcinoma, and no any histologic patterns were paticular to the each groups. The induction rate of mammary cancer was as follows: non-operated controls 80%, ovariectomized controls 0%, ovariectomized and estrogen-treated groups; 0.4μg. -injected 0%,1pg-implanted 30%,20μg-injected 17%, ovariectomized and progesterone-tr eated groups; 4mg-injected 38%,4mg-implanted 10%, and ovariectomized and E and P-treated groups; E 0.4μg +P 4. mg-injected 38%, E 1pg + P 4 mg-implanted 22%, E 20μg P 4 mg-injected 0%. In summary, D MBA-carcinogenesis on the mammary ducts in 3 months after the carcinogenadministration were suppressed completely by ovariectomy, provocated by moderate stimuli of estrogen or progesterone sole at the initiation stage, and inhibited by strong stimuli of estrogen during the initiation process. The role of exogeneous ovarian hormones in initiating the induction of mammary cancer on the ovariectomized and DMBA-injected animals were discussed.