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 journalArticlepeer-review

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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