title: A study of the structural basis of the carcinogenicity of tamoxifen, toremifene and their metabolites.
abstract: An analysis of the chemical structure of tamoxifen, toremifene and their metabolites indicates that metabolism to a DNA-reactive hydroxylamine intermediate is possible. The parent compounds and many of their metabolites are predicted to be rodent carcinogens. Moreover, many of these metabolites contain a 6 A or 8.4 A distance descriptor biphore. These geometric descriptors may be related to an ability of these chemicals to bind to an estrogen receptor. The prediction of the carcinogenicity of toremifene is not in accord with studies published thus far. However, the reports available have not excluded this possibility, since the protocols used have not addressed it systematically.
authors.affiliation: Department of Environmental and Occupational Health University of Pittsburgh, PA 15238, USA.
authors.forename: A
authors.initials: A
authors.lastname: Cunningham
authors.forename: G
authors.initials: G
authors.lastname: Klopman
authors.forename: H S
authors.initials: HS
authors.lastname: Rosenkranz
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017312:Toremifene / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D002273:Carcinogens; D013629:Tamoxifen; D017312:Toremifene