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.

中文翻译：

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7-谷胱甘肽-吡咯和7-半胱氨酸-吡咯是吡咯烷核生物碱的潜在致癌代谢产物。

许多吡咯并立烷生物碱（PAs）具有肝毒性，遗传毒性和致癌性。体内PA的代谢产生了四个（±）-6,7-二氢-7-羟基-1-羟甲基-5H-吡咯烷嗪（DHP）-DNA加合物，已被认为可引起PA诱导的大鼠肝肿瘤形成。在本研究中，我们确定将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，会形成同一组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PA的反应性代谢产物，可以与细胞DNA结合形成HepG2细胞中的DHP-DNA加合物，并有可能引发肝肿瘤的形成。