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In vitro toxicological evaluation of ethyl carbamate in human HepG2 cells

机译:氨基甲酸乙酯对人HepG2细胞的体外毒理学评价

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摘要

Ethyl carbamate (EC) is a multi-site carcinogen in experiment animals and probably carcinogenic to humans (IARC group 2A). The present study was designed to investigate the cytotoxicity effect of EC on human hepatoma G2 (HepG2) cells. The results revealed that EC inhibited the viability of HepG2 cells significantly in a dose-dependent manner. Further analysis indicated that high concentration of EC induced cell apoptosis, inhibited the G1 to S phase transition along with increased expression of p53 and p21 and decreased the expression of cyclin E and Cdk 2, but no significant change in p27 expression was observed, which were evidenced by both real time PCR and western blotting analyses. Moreover, the results of the DCFH-DA assay suggested that oxidative stress was involved in the cytotoxic effects of EC. Altogether, the present work indicated that p21, cyclin E and Cdk2, which were regulated by p53, might account for the effect of EC on cell viability and cell cycle arrest, but p27 was not involved in the pathway in HepG2 cells treated with EC.
机译:氨基甲酸乙酯(EC)是实验动物中的多部位致癌物,可能对人类具有致癌性(IARC 2A组)。本研究旨在研究EC对人肝癌G2(HepG2)细胞的细胞毒性作用。结果表明,EC以剂量依赖性方式显着抑制HepG2细胞的活力。进一步的分析表明,高浓度的EC诱导细胞凋亡,抑制了G1至S相的转变,同时增加了p53和p21的表达,并降低了cyclin E和Cdk 2的表达,但未观察到p27表达的显着变化。实时PCR和Western印迹分析均证明了这一点。而且,DCFH-DA测定的结果表明氧化应激与EC的细胞毒性作用有关。总之,目前的工作表明,受p53调节的p21,cyclin E和Cdk2可能解释了EC对细胞活力和细胞周期阻滞的影响,但p27不参与经EC处理的HepG2细胞的途径。

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