Synthetic estrogens and tamoxifen as promoters of hepatocarcinogenesis

James D. Yager, Yuenian E. Shi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)27-37
Number of pages11
JournalPreventive Medicine
Volume20
Issue number1
DOIs
StatePublished - Jan 1991

ASJC Scopus subject areas

  • Epidemiology
  • Public Health, Environmental and Occupational Health

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