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  2. Pyrrolizidine alkaloid-derived DNA adducts are common toxicological biomarkers of pyrrolizidine alkaloid N-oxides

Pyrrolizidine alkaloid-derived DNA adducts are common toxicological biomarkers of pyrrolizidine alkaloid N-oxides

  • J Food Drug Anal. 2017 Oct;25(4):984-991. doi: 10.1016/j.jfda.2017.09.001.
Xiaobo He 1 Qingsu Xia 1 Kellie Woodling 1 Ge Lin 2 Peter P Fu 1
Affiliations

Affiliations

  • 1 National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, United States.
  • 2 School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
Abstract

There are 660 Pyrrolizidine Alkaloids (PAs) and PA N-oxides present in the Plants, with approximately half being possible carcinogens. We previously reported that a set of four PA-derived DNA adducts is formed in the liver of rats administered a series of hepatocarcinogenic PAs and a PA N-oxide. Based on our findings, we hypothesized that this set of DNA adducts is a common biological biomarker of PA-induced liver tumor formation. In this study, we determined that rat liver microsomal metabolism of five hepatocarcinogenic PAs (lasiocarpine, retrorsine, riddelliine, monocrotaline, and heliotrine) and their corresponding PA N-oxides produced the same set of DNA adducts. Among these compounds, lasiocarpine N-oxide, retrorsine N-oxide, monocrotaline N-oxide, and heliotrine N-oxide are for first time shown to be able to produce these DNA adducts. These results further support the role of these DNA adducts as potential common biomarkers of PA-induced liver tumor initiation.

Keywords

DHP–DNA adducts; LC–ES–MS/MS; Pyrrolizidine alkaloid; Pyrrolizidine alkaloid N-oxide.

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