Genotoxicity of acrylamide in human hepatoma G2 (HepG2) cells
Genotoxicity of acrylamide in human hepatoma G2 (HepG2) cells
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DOI：
10.1016/j.tiv.2007.06.011
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发表时间：
2007-12-01
影响因子：
3.2
通讯作者：
Zhong, Laifu
中科院分区：
文献类型：
--
作者：
Jiang, Liping;Cao, Jun;Zhong, Laifu
最近发现，丙烯酰胺（AA）是动物实验中的一种致癌物质，也可能是一种人类致癌物质，在烹饪过程中在食物中形成，引起了人类健康问题。饮食暴露与人类的相关性仍存在争议。本研究的目的是使用单细胞凝胶电泳（SCGE）测定和微核试验（MNT）评估丙烯酰胺对人肝癌G2（HepG2）细胞（一种与检测遗传毒性/抗原毒性物质密切相关的细胞系）中可能的遗传毒性。为了阐明潜在机制，我们通过 8-羟基脱氧鸟苷 (8-OHdG) 的免疫细胞化学分析评估了细胞内活性氧 (ROS) 的生成和氧化 DNA 损伤的水平。通过用丁硫氨酸亚磺酰亚胺 (BSO) 处理以消耗 GSH，检查了谷胱甘肽 (GSH) 在 AA 诱导的氧化应激中的参与情况。结果表明，AA 以剂量依赖性方式引起 HepG2 细胞中 DNA 链断裂和 MN 频率增加。可能的机制是 AA 处理的 HepG2 细胞中 ROS 水平增加、GSH 消耗和 8-OHdG 形成增加。我们得出结论，AA 在 HepG2 细胞中发挥基因毒性作用，可能是通过细胞内 ROS 和 GSH 消耗诱导的氧化 DNA 损伤。 (C) 2007 Elsevier Ltd. 保留所有权利。
The recent finding that acrylamide (AA), a carcinogen in animal experiments and a probable human carcinogen, is formed in foods during cooking raises human health concerns. The relevance of dietary exposure for humans is still under debate. The purpose of the study was to evaluate the possible genotoxicity of acrylamide in human hepatoma G2 (HepG2) cells, a cell line of great relevance to detect genotoxic/antigenotoxic substances, using single cell gel electrophoresis (SCGE) assay and micronucleus test (MNT). In order to clarify the underlying mechanism(s) we evaluated the intracellular generation of reactive oxygen species (ROS) and the level of oxidative DNA damage by immunocytochemical analysis of 8-hydroxydeoxyguanosine (8-OHdG). The involvement of glutathione (GSH) in the AA-induced oxidative stress was examined through treatment with buthionine sulfoximine (BSO) to deplete GSH. The results indicate that AA caused DNA strand breaks and increase in frequency of MN in HepG2 cells in a dose-dependent manner. The possible mechanism underlies the increased levels of ROS, depletion of GSH and increase of 8-OHdG formation in HepG2 cells treated with AA. We conclude that AA exerts genotoxic effects in HepG2 cells, probably through oxidative DNA damage induced by intracellular ROS and depletion of GSH. (C) 2007 Elsevier Ltd. All rights reserved.