There are 660 pyrrolizidine alkaloids (PAs) and PA N-oxides present in the plants, with approximately half being possible carcinogens. We previously reported that a set of four PA-derived DNA adducts is formed in the liver of rats administered a series of hepatocarcinogenic PAs and a PA N-oxide. Based on our findings, we hypothesized that this set of DNA adducts is a common biological biomarker of PA-induced liver tumor formation. In this study, we determined that rat liver microsomal metabolism of five hepatocarcinogenic PAs (lasiocarpine, retrorsine, riddelliine, monocrotaline, and heliotrine) and their corresponding PA N-oxides produced the same set of DNA adducts. Among these compounds, lasiocarpine N-oxide, retrorsine N-oxide, monocrotaline N-oxide, and heliotrine N-oxide are for first time shown to be able to produce these DNA adducts. These results further support the role of these DNA adducts as potential common biomarkers of PA-induced liver tumor initiation.

中文翻译：

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吡咯里西啶生物碱衍生的 DNA 加合物是吡咯里西啶生物碱 N-氧化物的常见毒理学生物标志物

植物中存在 660 种吡咯里西啶生物碱 (PA) 和 PA N-氧化物，其中大约一半是可能的致癌物。我们之前报道过，在大鼠的肝脏中形成了一组四种 PA 衍生的 DNA 加合物，这些加合物被施用了一系列致癌 PA 和 PA N-氧化物。根据我们的发现，我们假设这组 DNA 加合物是 PA 诱导的肝肿瘤形成的常见生物标志物。在这项研究中，我们确定了五种致癌 PA（lasiocarpine、retrorsine、riddelliine、野百合碱和 heliotrine）及其相应的 PA N-氧化物的大鼠肝微粒体代谢产生了相同的 DNA 加合物。在这些化合物中，lasiocarpine N-氧化物、retrorsine N-氧化物、野百合碱 N-氧化物和 heliotrine N-氧化物首次被证明能够产生这些 DNA 加合物。