Intrinsic reactivity of tamoxifen and toremifene metabolites with DNA

Utha Hellmann-Blumberg, Maralee G. Cartner, Gregory T. Wurz, Michael W. DeGregorio

Research output: Contribution to journalArticle

16 Scopus citations


The antiestrogen tamoxifen is known to cause liver cancer in rats. This may be due to the formation of abundant DNA adducts in rat liver. A likely precursor to some of the tamoxifen adducts in rats is α-hydroxytamoxifen. It is not clear whether the rat data are relevant to human exposure. In the present study, we show that one of the major metabolites in humans reacts with double-stranded DNA in vitro in the absence of any metabolizing enzymes or activating chemicals. At least two distinct adduct spots resulting from 4-hydroxy-N-desmethyltamoxifen (metabolite Bx) were detected by 32P postlabeling and thin layer chromatography. The adduct level increases dramatically when metabolite Bx is irradiated with UV light to fuse into a phenanthrene ring system. 4-hydroxy-N-desmethyltoremifene, which differs from Bx by a single chlorine atom, forms fewer DNA adducts without irradiation but similar amounts after irradiation. These results suggest that the chlorine atom may interfere with drug-DNA interactions which facilitate adduct formation.

Original languageEnglish (US)
Pages (from-to)135-141
Number of pages7
JournalBreast Cancer Research and Treatment
Issue number2
StatePublished - 1998


  • DNA adducts
  • Metabolites
  • Postlabeling
  • Tamoxifen
  • Toremifene

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Hellmann-Blumberg, U., Cartner, M. G., Wurz, G. T., & DeGregorio, M. W. (1998). Intrinsic reactivity of tamoxifen and toremifene metabolites with DNA. Breast Cancer Research and Treatment, 50(2), 135-141.