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- Title
7-N-Acetylcysteine-pyrrole conjugate--A potent DNA reactive metabolite of pyrrolizidine alkaloids.
- Authors
Xiaobo He; Liang Ma; Qingsu Xia; Peter P. Fu
- Abstract
Plants containing pyrrolizidine alkaloids (PAs) are widespread throughout the world and are the most common poisonous plants affecting livestock, wildlife, and humans. PAs require metabolic activation to form reactive dehydropyrrolizidine alkaloids (dehydro-PAs) that are capable of alkylating cellular DNA and proteins, form (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-DNA and DHP-protein adducts, and lead to cytotoxicity, genotoxicity, and tumorigenicity. In this study, we determined that the metabolism of riddelliine and monocrotaline by human and rat liver microsomes in the presence of N-acetylcysteine both produced 7-N-acetylcysteine-DHP (7-NAC-DHP) and DHP. Reactions of 7-NAC-DHP with 2'-deoxyguanosine (dG), 2'-deoxyadenosine (dA), and calf thymus DNA in aqueous solution followed by enzymatic hydrolysis yielded DHP-dG and/or DHP-dA adducts. These results indicate that 7-NAC-DHP is a reactive metabolite that can lead to DNA adduct formation.
- Subjects
DNA metabolism; ALKALOIDS; RESEARCH methodology; PLANTS
- Publication
Journal of Food & Drug Analysis, 2016, Vol 24, Issue 4, p682
- ISSN
1021-9498
- Publication type
Article
- DOI
10.1016/j.jfda.2016.08.001