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

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.

• Authors: Xiaobo He, Qingsu Xia, Kellie Woodling, Ge Lin, Peter P Fu
• Journal: Journal of food and drug analysis (J Food Drug Anal) Vol. 25 Issue 4 Pg. 984-991 (Oct 2017) ISSN: 2224-6614 [Electronic] China (Republic : 1949- )
• PMID: 28987376 (Publication Type: Journal Article)
• Copyright: Copyright © 2017. Published by Elsevier B.V.

Chemical References

• Biomarkers
• DNA Adducts
• Pyrrolizidine Alkaloids
• DNA

Topics

• Animals
• Biomarkers (metabolism)
• Cattle
• DNA
• DNA Adducts (chemistry, genetics, metabolism)
• Male
• Microsomes, Liver (drug effects, metabolism)
• Pyrrolizidine Alkaloids (chemistry, toxicity)
• Rats, Inbred F344