CHEMOPREVENTIVE EFFECTS OF TAMOXIFEN IN ETHYL METHANESULFONATE-INDUCED RAT MAMMARY CARCINOGENESIS

Ethyl methanesulphonate (EMS), an alkylating agent and a potent mutage n, has been shown to be an effective carcinogen for the induction of m ammary carcinoma in female Wistar King A rats. We therefore utilized t his new system to assess the effects of tamoxifen (TAM) on mammary car cinogenesis. In Group A rats, given EMS orally for a period of 12 week s, mammary carcinomas were first detected at the 13th week and were fo und in all surviving rats at the 20th week. The concomitant administra tion of TAM for 4 weeks, in Group B rats, retarded the development of the tumors significantly. There was a significant reduction in the inc idence of estrogen receptor (ER)-positive tumors in the rats previousl y exposed to TAM; 100% in Group A versus 50% in Group B. Neither the p rogesterone receptor (PgR) nor androgen receptor (AR) status of the tu mors were significantly different between these two groups. The inhibi tory effects of TAM on tumor induction was also observed when TAM trea tment started after EMS administration, though the intensity was small er than that in Group B. These findings suggest the preventive action of TAM on EMS-induced mammary carcinogenesis, and indicate that this t umor system may provide a feasible model for research on chemopreventi on and hormone therapy using an antiestrogen for human mammary carcino ma.