title: Analysis of tamoxifen-DNA adducts in endometrial explants by MS and 32P-postlabeling.
abstract: The nonsteroidal antiestrogen tamoxifen increases the risk of endometrial cancer; however, the mechanism for the induction of these tumors is not known. Recently, Sharma et al. [Biochem. Biophys. Res. Commun. 307 (2003) 157], using high performance liquid chromatography (HPLC) with online postcolumn photochemical activation and fluorescence detection, reported the presence of (E)-alpha-(deoxyguanosin- N2-yl)tamoxifen in DNA from human endometrial explants incubated with tamoxifen. Inasmuch as the methodology used by these investigators does not allow unambiguous characterization of tamoxifen-DNA adducts, we have used two additional techniques (HPLC coupled with electrospray ionization tandem mass spectrometry and 32P-postlabeling analyses) to assay for the presence of tamoxifen-DNA adducts in the human endometrial explant DNA. Tamoxifen-DNA adducts were not detected by either method.
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA. fbeland@nctr.fda.gov
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Beland
authors.forename: Mona I
authors.initials: MI
authors.lastname: Churchwell
authors.forename: Alan
authors.initials: A
authors.lastname: Hewer
authors.forename: David H
authors.initials: DH
authors.lastname: Phillips
authors.forename: Gonçalo
authors.initials: G
authors.lastname: Gamboa da Costa
authors.forename: M Matilde
authors.initials: MM
authors.lastname: Marques
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000187:drug effects*; D018736:DNA Adducts / Q000032:analysis*; D004717:Endometrium / Q000737:chemistry*; D005260:Female; D006801:Humans; D010761:Phosphorus Radioisotopes; D013050:Spectrometry, Fluorescence; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013629:Tamoxifen / Q000032:analysis / Q000494:pharmacology*
chemical_list: D018736:DNA Adducts; D010761:Phosphorus Radioisotopes; D013629:Tamoxifen; D004247:DNA