Antioxidant inhibits tamoxifen-DNA adducts in endometrial explant culture

Minoti Sharma, David E. Shubert, Moheswar Sharma, Kerry J. Rodabaugh, Barbara P. McGarrigle, Chad M. Vezina, Diane P. Bofinger, James R. Olson

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Fresh human endometrial explants were incubated for 24h at 37°C with either tamoxifen (10-100μM) or the vehicle (0.1% ethanol). Three metabolites namely, α-hydroxytamoxifen, 4-hydroxytamoxifen, and N-desmethyltamoxifen were identified in the culture media. Tissue size was limited but DNA adducts formed by the α-hydroxytamoxifen pathway were detected using authentic α-(deoxyguanosyl-N2) tamoxifen standards. Relative DNA-adduct levels of 2.45, 1.12, and 0.44 per 106 nucleotides were detected following incubations with 100, 25, and 10μM tamoxifen, respectively. The concurrent exposure of the explants to 100μM tamoxifen with 1mM ascorbic acid reduced the level of α-hydroxytamoxifen substantially (68.9%). The formation of tamoxifen-DNA adducts detectable in the explants from the same specimens exposed to 100μM tamoxifen with 1mM ascorbic acid were also inhibited. These results support the role of oxidative biotransformation of tamoxifen in the subsequent formation of DNA adducts in this tissue.

Original languageEnglish (US)
Pages (from-to)157-164
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume307
Issue number1
DOIs
StatePublished - Jul 18 2003

Keywords

  • Antioxidant
  • Explant culture
  • Human endometrial tissue
  • Tamoxifen metabolites
  • Tamoxifen-DNA adducts

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Sharma, M., Shubert, D. E., Sharma, M., Rodabaugh, K. J., McGarrigle, B. P., Vezina, C. M., Bofinger, D. P., & Olson, J. R. (2003). Antioxidant inhibits tamoxifen-DNA adducts in endometrial explant culture. Biochemical and Biophysical Research Communications, 307(1), 157-164. https://doi.org/10.1016/S0006-291X(03)01134-3