砷是于环境中的强毒性重金属,会导致人类和动物的健康问题,包括肝的疾病.长期暴露于砷仍然是世界范围内的环境健康问题,影响着数亿人.虽然砷诱导的氧化应激和细胞凋亡已被证实,但其潜在细胞凋亡机制尚未完全阐明.本研究旨在探讨亚砷酸钠(sodium arsenite,SA)诱导的肝中毒是否与DNA复制和修复途径的调节有关.MTT法和镜检法结果显示,SA对人肝细胞(L02)细胞增殖有抑制作用,而这种作用具有一定的时间及浓度依赖性.流式细胞仪检测不同浓度SA对L02细胞的影响,与对照组相比,高浓度的SA显著影响了L02细胞周期.此外,RNA测序结果表明,SA处理后的细胞差异表达基因集中在DNA复制过程和修复通路方面.同时,蛋白质印迹及实时定量PCR结果显示,SA可影响人RecQ DNA解旋酶和修复基因的表达,在我们的研究中,SA被证明在体外能抑制细胞增殖,诱导细胞凋亡,引起DNA损伤并阻止人肝细胞L02的细胞周期.基于以上结果表明,砷中毒可能与DNA复制和修复途径的调节有关,这为了解砷中毒的分子机制提供了思路.“,”Arsenic is a potent toxic heavy metal found in the environment that can causes health problems,including liver disease in humans and animals.Chronic exposure to arsenic remains an environmental health problem worldwide,affecting hundreds of millions of people.Although the oxidative stress and apoptosis induced by arsenic have been confirmed,the underlying mechanism of apoptosis has not been fully elucidated.The purpose of this study is to investigate whether sodium arsenite (SA)-induced liver toxicity is related to the regulation of DNA replication and repair pathways.The results of MTT and microscopy showed that SA has an inhibitory effect on the proliferation of human hepatocytes(L02),and this effect is time and concentration dependent.Flow cytometry detected the effects of different concentrations of SA on L02 cells.Compared with the control group,high concentrations of SA significantly affected the L02 cell cycle.In addition,RNA sequencing results showed that the differentially expressed genes in cells after SA treatment were concentrated in the DNA replication process and repair pathways.The effect of SA treatment on the expression of human RECQ DNA helicase and repair genes was further confirmed by Western blot and real-time quantitative PCR.In vitro study showed that SA treatment inhibited cell proliferation,and induced apoptosis as well as DNA damage and cell cycle arrest of human liver cell L02.Collectively,these results indicate that arsenic poisoning is related to the regulation of DNA replication and repair pathways,which provides insight for understanding the molecular mechanism of arsenic poisoning.