Analysis of tamoxifen-DNA adducts in endometrial explants by MS and 32P-postlabeling

被引:15
作者
Beland, FA [1 ]
Churchwell, MI
Hewer, A
Phillips, DH
da Costa, GG
Marques, MM
机构
[1] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA
[2] Inst Canc Res, Sutton SM2 5NG, Surrey, England
[3] Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-104900 Lisbon, Portugal
关键词
tamoxifen; P-32-postlabeling; HPLC; electrospray ionization tandem mass spectrometry; DNA adducts; endometrial cancer;
D O I
10.1016/j.bbrc.2004.05.168
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 a]. [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-N-2-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 P-32-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. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:297 / 302
页数:6
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