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首页> 外文期刊>Mutation Research - Genetic Toxicology and Environmental Mutagenesis >Induction of sister chromatid exchange by acrylamide and glycidamide in human lymphocytes: Role of polymorphisms in detoxification and DNA-repair genes in the genotoxicity of glycidamide
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Induction of sister chromatid exchange by acrylamide and glycidamide in human lymphocytes: Role of polymorphisms in detoxification and DNA-repair genes in the genotoxicity of glycidamide

机译：丙烯酰胺和缩水甘油酰胺在人淋巴细胞中诱导姐妹染色单体交换：多态性在解毒和DNA修复基因中对缩水甘油酰胺遗传毒性的作用

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摘要

Acrylamide (AA) is a probable human carcinogen generated in carbohydrate-rich foodstuffs upon heating. Glycidamide (GA), formed via epoxidation, presumably mediated by cytochrome P450 2E1, is considered to be the active metabolite that plays a central role in the genotoxicity of AA. The aim of this work was to evaluate the cytogenetic damage induced by AA and GA in cultured human lymphocytes by use of the sister chromatid exchange (SCE) assay. Furthermore, this report addresses the role of individual genetic polymorphisms in key genes involved in detoxification and DNA-repair pathways (BER, NER, HRR and NHEJ) on the induction of SCE by GA. While AA induced the number of SCE/metaphase only slightly, especially for the highest concentration tested (2000 μM), GA markedly induced SCEs in a concentration-dependent manner up to concentrations of 750 μM, leading to an increase in SCEs of up to about 10-fold compared with controls. By combining DNA damage in GA-treated lymphocytes and data on polymorphisms, associations between the induction of SCEs with GSTP1 (Ile105Val) and GSTA2 (Glu210Ala) genotypes are suggested.
机译：丙烯酰胺（AA）是一种可能的人类致癌物，加热后会在富含碳水化合物的食品中产生。通过环氧化作用形成的糖苷酰胺（GA）被认为是由细胞色素P450 2E1介导的，被认为是活性代谢产物，在AA的遗传毒性中起着关键作用。这项工作的目的是通过使用姐妹染色单体交换（SCE）分析评估AA和GA在培养的人淋巴细胞中引起的细胞遗传学损害。此外，本报告还探讨了个体遗传多态性在涉及解毒和DNA修复途径的关键基因（BER，NER，HRR和NHEJ）在GA诱导SCE中的作用。虽然AA只能轻微诱导SCE /中期的数量，特别是对于最高测试浓度（2000μM），GA却以浓度依赖的方式显着诱导SCE，直至浓度达到750μM，导致SCE的增加高达大约是对照的10倍。通过结合GA处理的淋巴细胞中的DNA损伤和多态性数据，建议将SCEs诱导与GSTP1（Ile105Val）和GSTA2（Glu210Ala）基因型联系起来。

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