Tandem Mass Spectrometry Analysis of N2-(trans-Isoestragol-3'-yl)-2'-deoxyguanosine as a Strategy to Study Species Differences in Sulfotransferase Conversion of the Proximate

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• 作者：Ans Punt ; Thierry Delatour ; Gabriele Scholz ; Benoî ; t Schilter ; Peter J. van Bladeren ; Ivonne M. C. M. Rietjens
• 刊名：Chemical Research in Toxicology
• 出版年：2007
• 出版时间：July 2007
• 年：2007
• 卷：20
• 期：7
• 页码：991 - 998
• 全文大小：116K
• 年卷期：v.20,no.7(July 2007)
• ISSN：1520-5010

文摘

To get more insight into possible species differences in the bioactivation of estragole, the kinetics forsulfonation of the proximate carcinogen 1'-hydroxyestragole were compared for male rat, male mouse,and mixed gender human liver S9 homogenates. In order to quantify sulfonation, 2'-deoxyguanosine wasadded to the incubation mixture in which sulfonation of 1'-hydroxyestragole was catalyzed to trap thereactive 1'-sulfooxyestragole. A method was developed with which the formation of the most abundantadduct with 2'-deoxyguanosine could be quantified using isotope dilution LC-ESI-MS/MS. Comparingthe kinetics for sulfonation by liver S9 homogenates of male rat, male mouse, and humans revealed thatsulfonation was about 30 times more efficient by male rat liver S9 than by human liver S9, whereas thecatalytic efficiency by male mouse and human liver S9 was about the same. This indicates, as far as thebioactivation by sulfotransferase is concerned, that when extrapolating the cancer risk from laboratoryanimals to humans, using data from male rats may overestimate the cancer risk in humans, whereasusing data from male mice may provide a better estimate of the cancer risk in humans.