Analysis of tamoxifen-DNA adducts in endometrial explants by MS and 32P-postlabeling.
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.
Beland
Frederick A
FA
Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA. fbeland@nctr.fda.gov
Churchwell
Mona I
MI
Hewer
Alan
A
Phillips
David H
DH
Gamboa da Costa
Gonçalo
G
Marques
M Matilde
MM
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*
D018736:DNA Adducts; D010761:Phosphorus Radioisotopes; D013629:Tamoxifen; D004247:DNA