Chemopreventive effects of tamoxifen in ethyl methanesulphonate-induced rat mammary carcinogenesis.
Ethyl methanesulphonate (EMS), an alkylating agent and a potent mutagen, has been shown to be an effective carcinogen for the induction of mammary carcinoma in female Wistar King A rats. We therefore utilized this new system to assess the effects of tamoxifen (TAM) on mammary carcinogenesis. In Group A rats, given EMS orally for a period of 12 weeks, mammary carcinomas were first detected at the 13th week and were found in all surviving rats at the 20th week. The concomitant administration of TAM for 4 weeks, in Group B rats, retarded the development of the tumors significantly. There was a significant reduction in the incidence of estrogen receptor (ER)-positive tumors in the rats previously exposed to TAM; 100% in Group A versus 50% in Group B. Neither the progesterone receptor (PgR) nor androgen receptor (AR) status of the tumors were significantly different between these two groups. The inhibitory effects of TAM on tumor induction was also observed when TAM treatment started after EMS administration, though the intensity was smaller than that in Group B. These findings suggest the preventive action of TAM on EMS-induced mammary carcinogenesis, and indicate that this tumor system may provide a feasible model for research on chemoprevention and hormone therapy using an antiestrogen for human mammary carcinoma.
Department of Surgery, Kyushu University, Beppu, Japan.
H
H
Ueo
H
H
Matsuoka
M
M
Honda
H
H
Inoue
R
R
Takaki
T
T
Akiyoshi
D000818:Animals; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced* / Q000517:prevention & control; D008698:Mesylates / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D013629:Tamoxifen / Q000494:pharmacology*; D013997:Time Factors
D008698:Mesylates; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; C045880:methanesulfonic acid