Quantitation of DNA reactive pyrrolic metabolites of senecionine - A carcinogenic pyrrolizidine alkaloid by LC/MS/MS analysis.

Abstract

Pyrrolizidine alkaloids (PAs) are carcinogenic phytochemicals, inducing liver tumors in experimental rodents. We previously determined that (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP), 7-glutathione-DHP, 7-cysteine-DHP, 7-N-acetylcysteine-DHP, and 1-CHO-DHP are DNA reactive pyrrolic metabolites potentially associated with PA-induced liver tumor initiation. In this study, we developed an LC/MS/MS multiple reaction monitoring (MRM) mode method to identify and quantify these metabolites formed from the metabolism of senecionine, a carcinogenic PA, by mouse, rat, and human liver microsomes, and primary rat hepatocytes. Together with the chemically prepared standards of these metabolites, this represents an accurate and convenient LC/MS/MS analytical method for quantifying these five reactive pyrrolic metabolites in biological systems.

• Authors: Qingsu Xia, Xiaobo He, Qiang Shi, Ge Lin, Peter P Fu
• Journal: Journal of food and drug analysis (J Food Drug Anal) Vol. 28 Issue 1 Pg. 167-174 (01 2020) ISSN: 2224-6614 [Electronic] China (Republic : 1949- )
• PMID: 31883605 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright © 2019. Published by Elsevier Taiwan LLC.

Chemical References

• Carcinogens
• DNA Adducts
• Pyrroles
• Pyrrolizidine Alkaloids
• DNA
• senecionine

Topics

• Animals
• Carcinogens (analysis)
• Cells, Cultured
• Chromatography, Liquid
• DNA
• DNA Adducts
• Hepatocytes (drug effects)
• Humans
• Mice
• Microsomes, Liver (drug effects)
• Pyrroles
• Pyrrolizidine Alkaloids (analysis)
• Rats
• Tandem Mass Spectrometry