7-Glutathione-pyrrole and 7-cysteine-pyrrole are potential carcinogenic metabolites of pyrrolizidine alkaloids. (3rd April 2017)

• Record Type: Journal Article
• Authors: He, Xiaobo; Xia, Qingsu; Fu, Peter P.
• Is Part Of: Journal of environmental science and health. Volume 35:Number 2(2017)
• Page Start: 69
• Page End: 83
• Publication Date: 2017-04-03
• Subjects: Pyrrolizidine alkaloid -- DHP -- 7-GS-DHP -- 7-cysteine-DHP -- DNA adducts; Carcinogenesis -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmentally induced diseases -- Periodicals; Environmental Health -- periodicals; Carcinogens, Environmental -- periodicals; Hazardous Substances -- periodicals; 616.994071
• DOI: 10.1080/10590501.2017.1298358
• Languages: English
• ISSNs: 1059-0501

Abstract

ABSTRACT: Many pyrrolizidine alkaloids (PAs) are hepatotoxic, genotoxic, and carcinogenic phytochemicals. Metabolism of PAs in vivo generates four (±)-6, 7-dihydro-7-hydroxy-1-hydroxymethyl-5 H -pyrrolizine (DHP)-DNA adducts that have been proposed to be responsible for PA-induced liver tumor formation in rats. In this present study, we determined that the same set of DHP-DNA adducts was formed upon the incubation of 7-glutathione-DHP and 7-cysteine-DHP with cultured human hepatocarcinoma HepG2 cells. These results suggest that 7-glutathione-DHP and 7-cysteine-DHP are reactive metabolites of PAs that can bind to cellular DNA to form DHP-DNA adducts in HepG2 cells, and can potentially initiate liver tumor formation.