Chemoprevention of breast cancer by tamoxifen: risks and opportunities.
The antioestrogen tamoxifen is of proven efficacy in inhibiting the growth of oestrogen receptor positive breast cancers in women. In rats, long-term dosing leads to the development of hepatocellular tumours. Tamoxifen in this species is a genotoxic carcinogen. Metabolic activation by cytochrome P450-dependent enzymes leads to DNA damage detectable by 32P-postlabelling. Factors important in the development of hepatocellular lesions were the nature and quantity of metabolism and promotion/progression of the DNA lesion by agents such as phenobarbital and cell proliferation. No evidence was found for tamoxifen-induced DNA damage in the livers of 7 women taking this drug therapeutically.
Smith
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MRC Toxicology Unit, University of Leicester, UK.
White
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IN
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001711:Biotransformation; D001943:Breast Neoplasms / Q000517:prevention & control*; D004249:DNA Damage; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051381:Rats; D013629:Tamoxifen / Q000493:pharmacokinetics / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D004965:Estrogen Antagonists; D013629:Tamoxifen