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首页> 外文期刊>Toxicology Letters: An International Journal Providing a Forum for Original and Pertinent Contributions in Toxicology Research >New insights into the molecular mechanisms of chemical carcinogenesis: In vivo adduction of histone H2B by a reactive metabolite of the chemical carcinogen furan
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New insights into the molecular mechanisms of chemical carcinogenesis: In vivo adduction of histone H2B by a reactive metabolite of the chemical carcinogen furan

机译:进入化学致癌物的分子机制的新见解:体内通过化学致癌物质呋喃的反应性代谢物的组蛋白H2B

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摘要

Furan is a rodent hepatocarcinogen ubiquitously found in the environment and heat-processed foods. Furan undergoes cytochrome P450 2E1-catalyzed bioactivation to cis-2-butene-1,4-dial (BDA), which has been shown to form an electrophilic conjugate (GSH-BDA) with glutathione. Both BDA and GSH-BDA yield covalent adducts with lysine residues in proteins. Dose-and time-dependent epigenetic histone alterations have been observed in furan-treated rats. While the covalent modification of histones by chemical carcinogens has long been proposed, histone-carcinogen adducts have eluded detection in vivo. In this study, we investigated if the covalent modification of histones by furan may occur in vivo prior to epigenetic histone alterations.
机译:呋喃是一种植物肝癌,普遍存在的环境和热处理食物。 Furan经历细胞色素P450 2E1催化的生物活化,向顺式-2-丁烯-1,4-转盘(BDA)已被证明形成与谷胱甘肽的亲电缀合物(GSH-BDA)。 BDA和GSH-BDA均产生与蛋白质中赖氨酸残基的共价加合物。 已经在呋喃处理的大鼠中观察到剂量和时间依赖性表观遗传组蛋白改变。 虽然已经提出了通过化学致癌物的组蛋白的共价修饰,但组蛋白 - 致癌物质加合物在体内突出检测。 在这项研究中,我们研究了呋喃的组织细胞的共价修饰,在表观遗传组蛋白改变之前可能在体内发生。

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