TY - JOUR
T1 - Synthetic estrogens and tamoxifen as promoters of hepatocarcinogenesis
AU - Yager, James D.
AU - Shi, Yuenian E.
N1 - Funding Information:
i The work reported in this manuscript was conducted while Drs. Shi and Yager were at the Dartmouth Medical School. This work was supported by NC1 Grant CA 36701. The Norris Cotton Cancer Center Support (CORE) Grant CA 23108 supported the use and maintenance of shared facilities and equipment. Y.E.S. was the recipient of a Friends of the Norris Cotton Cancer Center Predoctoral Fellowship. * Presented at the Workshop on Antiestrogen Prevention of Breast Cancer, October 2-3, 1989, Madison, WI. Proceedings cosponsored by the National Cancer Institute (Grant 1 R13 CA49561-01) and the American Cancer Society (Grant RD 291). 3 To whom requests for reprints should be addressed. 4 Abbreviations used: EE, ethinyl estradiol; GGT+ , y-glutamyl transpeptidase positive; DEN, diethylnitrosamine; EGF, epidermal growth factor; T, tamoxifen; PB, phenobarbital; TPA, 12-0-tetradecanoylphorbol-13-acetate; OC, oral contraceptive.
PY - 1991/1
Y1 - 1991/1
N2 - Previously, we demonstrated that the synthetic estrogens mestranol and ethinyl estradiol (EE) were strong promoters of hepatocarcinogenesis initiated in intact female rats by prior treatment with diethylnitrosamine (J. D. Yager, H. A. Campbell, D. S. Longnecker, B. D. Roebuck, and M. C. Benoit, Cancer Res. 1984; 44:3862-3869). In subsequent studies designed to elucidate possible mechanisms of promotion by EE, we investigated whether the antiestrogen tamoxifen was antagonistic to the effects of EE (J. D. Yager, B. D. Roebuck, T. L. Paluszcyk, and V. A. Memoli, Carcinogenesis 1986; 7:2007-2014). In these and more recent studies we found that tamoxifen inhibited the stimulatory effects of EE on pituitary size, liver DNA synthesis, and, in cultured hepatocytes, the potentiation by EE of epidermal growth factor-induced DNA synthesis. Furthermore, tamoxifen also inhibited the ability of EE to promote hepatocarcinogenesis. However, paradoxically, tamoxifen alone enhanced the appearance of γ-glutamyl transpeptidase positive foci in diethylnitrosamine-initiated livers indicating that it is a promoter of hepatocarcinogenesis.
AB - Previously, we demonstrated that the synthetic estrogens mestranol and ethinyl estradiol (EE) were strong promoters of hepatocarcinogenesis initiated in intact female rats by prior treatment with diethylnitrosamine (J. D. Yager, H. A. Campbell, D. S. Longnecker, B. D. Roebuck, and M. C. Benoit, Cancer Res. 1984; 44:3862-3869). In subsequent studies designed to elucidate possible mechanisms of promotion by EE, we investigated whether the antiestrogen tamoxifen was antagonistic to the effects of EE (J. D. Yager, B. D. Roebuck, T. L. Paluszcyk, and V. A. Memoli, Carcinogenesis 1986; 7:2007-2014). In these and more recent studies we found that tamoxifen inhibited the stimulatory effects of EE on pituitary size, liver DNA synthesis, and, in cultured hepatocytes, the potentiation by EE of epidermal growth factor-induced DNA synthesis. Furthermore, tamoxifen also inhibited the ability of EE to promote hepatocarcinogenesis. However, paradoxically, tamoxifen alone enhanced the appearance of γ-glutamyl transpeptidase positive foci in diethylnitrosamine-initiated livers indicating that it is a promoter of hepatocarcinogenesis.
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U2 - 10.1016/0091-7435(91)90004-N
DO - 10.1016/0091-7435(91)90004-N
M3 - Article
C2 - 1672563
AN - SCOPUS:0026065862
SN - 0091-7435
VL - 20
SP - 27
EP - 37
JO - Preventive Medicine
JF - Preventive Medicine
IS - 1
ER -