氨基甲酸乙酯诱导HepG2细胞凋亡的分子机制

发酵食品中的氨基甲酸乙酯（ethyl carbamate，EC）是国际癌症研究机构认可的2A类可能致癌物。前期 研究表明EC可诱导人类HepG2细胞凋亡，但机理未明。本研究采用实时荧光定量聚合酶链式反应和蛋白免疫印迹 技术检测100 mmol/L EC处理对HepG2细胞凋亡通路基因的影响，以探索EC诱导人体细胞凋亡的分子机制。结果 表明：4 h EC处理在促进诱骗受体基因TNFRSF10D和促存活基因GADD45B表达的同时，激活细胞凋亡相关的线粒 体介导的内源通路和内质网应激通路基因的表达，EC对绝大多数受试基因的mRNA水平和蛋白水平的影响一致。 12 h EC处理显著提高凋亡相关基因的mRNA水平，同时显著降低大多数基因的蛋白表达水平，表明长时间EC处理 抑制了细胞内蛋白的合成。本研究结果为食源性EC的进一步风险评估提供了依据。

Molecular Mechanisms of Ethyl Carbamate-Induced Apoptosis in Human HepG2 Cells

Ethyl carbamate (EC) that is commonly found in fermented foods is regarded as a Group 2A carcinogen by the International Agency for Research on Cancer. Our previous study indicated that EC could induce apoptosis in human HepG2 cells; however, its molecular mechanisms remain unclear. In this study, we aim to explore the molecular mechanisms of EC-induced apoptosis in HepG2 cells using real-time quantitative PCR and Western blotting to examine the effects of 100 mmol/L EC treatment on the expression of apoptosis-related genes at both the mRNA and protein levels. The results showed that 4 h EC treatment increased the mRNA and protein levels of decoy receptor (TNFRSF10D), pro-survival (GADD45B), and apoptosis-related gene from the mitochondria mediated intrinsic and endoplasmic reticulum stress response pathways. In addition, 12 h EC treatment up-regulated significantly the mRNA levels of apoptosis-related genes, but down-regulated significantly the protein levels of most tested genes, indicating that long-term EC treatment can inhibit protein synthesis. This study can lay a solid foundation for further risk assessment of food-borne EC.