title: Clinical relevance of laboratory and animal data on tamoxifen.
abstract: Tamoxifen is being evaluated in clinical trials as a preventive agent in women at high risk for breast cancer. This new, potentially long-term therapeutic role has generated some concerns regarding safety, based on the results of animal studies that demonstrated an increased incidence of liver cancer in rats and the formation of DNA adducts. However, direct extrapolation of data from rats to risk estimates in women does not appear to be appropriate. Studies have shown that there are substantial species-related differences in activation and detoxication of tamoxifen that directly affect the formation of DNA adducts. This major species difference in DNA adduct formation appears to be the result of differences in metabolic activation and detoxication; humans form much less of the electrophilic metabolites that bind to DNA and rapidly detoxify those that are formed.
authors.affiliation: School of Medicine, University of North Carolina, Chapel Hill, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Swenberg
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D015197:Carcinogenicity Tests; D004247:DNA / Q000187:drug effects*; D018736:DNA Adducts; D006801:Humans; D007753:Laboratories; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D018736:DNA Adducts; D013629:Tamoxifen; D004247:DNA