Protective role of electrophile-reactive glutathione for DNA damage repair inhibitory effect of dibromoacetonitrile
Protective role of electrophile-reactive glutathione for DNA damage repair inhibitory effect of dibromoacetonitrile
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亲电子反应性谷胱甘肽对二溴乙腈 DNA 损伤修复抑制作用的保护作用
DOI：
10.1016/j.jes.2022.05.015
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发表时间：
2022
影响因子：
6.9
通讯作者：
Yuko Ibuki
中科院分区：
文献类型：
--
作者：
Yukako Komaki;Koki Suganuma;Yuko Ibuki
二溴乙腈（DBAN）是一种消毒副产物，与啮齿类动物的癌症有关，但其致癌机制尚未完全阐明。我们最近报道DBAN诱导核苷酸切除修复（NER）的抑制。在这项研究中，我们研究了谷胱甘肽（GSH）是否参与DBAN诱导的NER抑制。用L-丁硫氨酸-（S，R）-亚砜亚胺（BSO）预处理人角质形成细胞HaCaT以耗尽细胞内GSH。BSO处理显著增强DBAN诱导的NER抑制以及细胞内氧化。NER蛋白（转录因子IIH和着色性干皮病互补组G）的DNA损伤位点的招聘被DBAN抑制，这是进一步加剧BSO治疗。我们的研究结果表明，细胞内GSH保护细胞免受DBAN诱导的遗传毒性，包括抑制DNA损伤修复。
Dibromoacetonitrile (DBAN) is a disinfection byproduct (DBP) and linked with cancer in rodents, but the mechanism of its carcinogenicity has not been fully elucidated. We recently reported that DBAN induced inhibition of nucleotide excision repair (NER). In this study, we investigated if glutathione (GSH) is involved in the DBAN-induced inhibition of NER. Human keratinocytes HaCaT were pretreated with L-buthionine-(S,R)-sulfoximine (BSO) to deplete intracellular GSH. BSO treatment markedly potentiated the DBAN-induced NER inhibition as well as intracellular oxidation. The recruitment of NER proteins (transcription factor IIH, and xeroderma pigmentosum complementation group G) to DNA damage sites was inhibited by DBAN, which was further exacerbated by BSO treatment. Our results suggest that intracellular GSH protects cells from DBAN-induced genotoxicity including inhibition of DNA damage repair.