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 carcinogen 1'-hydroxyestragole

A. Punt, T. Delatour, G. Scholz, B. Schilter, P.J. van Bladeren, I.M.C.M. Rietjens

Research output: Contribution to journalArticleAcademicpeer-review

47 Citations (Scopus)

Abstract

To get more insight into possible species differences in the bioactivation of estragole, the kinetics for sulfonation 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 was added to the incubation mixture in which sulfonation of 1'-hydroxyestragole was catalyzed to trap the reactive 1'-sulfooxyestragole. A method was developed with which the formation of the most abundant adduct with 2'-deoxyguanosine could be quantified using isotope dilution LC-ESI-MS/MS. Comparing the kinetics for sulfonation by liver S9 homogenates of male rat, male mouse, and humans revealed that sulfonation was about 30 times more efficient by male rat liver S9 than by human liver S9, whereas the catalytic efficiency by male mouse and human liver S9 was about the same. This indicates, as far as the bioactivation by sulfotransferase is concerned, that when extrapolating the cancer risk from laboratory animals to humans, using data from male rats may overestimate the cancer risk in humans, whereas using data from male mice may provide a better estimate of the cancer risk in humans
Original languageEnglish
Pages (from-to)991-998
JournalChemical Research in Toxicology
Volume20
Issue number7
DOIs
Publication statusPublished - 2007

Keywords

  • naturally-occurring alkenylbenzenes
  • post-labeling analysis
  • dna-adducts
  • mouse-liver
  • b6c3f1 mice
  • estragole
  • safrole
  • 1'-hydroxyestragole
  • 1'-hydroxysafrole
  • metabolism

Fingerprint Dive into the research topics of '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 carcinogen 1'-hydroxyestragole'. Together they form a unique fingerprint.

Cite this