7-Glutathione-pyrrole and 7-cysteine-pyrrole are potential carcinogenic metabolites of pyrrolizidine alkaloids.

Q2 Biochemistry, Genetics and Molecular Biology

Journal of Environmental Science and Health Part C-Environmental Carcinogenesis & Ecotoxicology Reviews Pub Date : 2017-04-03 Epub Date: 2017-03-01 DOI:10.1080/10590501.2017.1298358

Xiaobo He, Qingsu Xia, Peter P Fu

引用次数: 21

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-5H-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.

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7-谷胱甘肽吡咯和7-半胱氨酸吡咯是吡咯利西啶类生物碱的潜在致癌代谢物。

许多吡咯利西啶生物碱(PAs)是肝毒性、遗传毒性和致癌的植物化学物质。PAs在体内代谢产生四种(±)-6,7-二氢-7-羟基-1-羟甲基- 5h -吡咯利嗪(DHP)-DNA加合物，这些加合物被认为是pa诱导大鼠肝脏肿瘤形成的原因。在本研究中，我们发现7-谷胱甘肽- dhp和7-半胱氨酸- dhp与培养的人肝癌HepG2细胞孵育后形成了相同的DHP-DNA加合物。这些结果表明，7-谷胱甘肽- dhp和7-半胱氨酸- dhp是PAs的反应性代谢物，可以结合细胞DNA在HepG2细胞中形成DHP-DNA加合物，并可能引发肝脏肿瘤的形成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Environmental Science and Health Part C-Environmental Carcinogenesis & Ecotoxicology Reviews 环境科学-毒理学

CiteScore

6.20

自引率

0.00%

发文量

审稿时长

>24 weeks

期刊介绍： Journal of Environmental Science and Health, Part C: Environmental Carcinogenesis and Ecotoxicology Reviews aims at rapid publication of reviews on important subjects in various areas of environmental toxicology, health and carcinogenesis. Among the subjects covered are risk assessments of chemicals including nanomaterials and physical agents of environmental significance, harmful organisms found in the environment and toxic agents they produce, and food and drugs as environmental factors. It includes basic research, methodology, host susceptibility, mechanistic studies, theoretical modeling, environmental and geotechnical engineering, and environmental protection. Submission to this journal is primarily on an invitational basis. All submissions should be made through the Editorial Manager site, and are subject to peer review by independent, anonymous expert referees. Please review the instructions for authors for manuscript submission guidance.