关键词: 氨基甲酸乙酯, HepG2细胞, 细胞凋亡, 内源途径, 内质网氧化应激, 外源途径

Abstract: 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.

Key words: ethyl carbamate, HepG2 cell, apoptosis, intrinsic pathway, endoplasmic reticulum stress, extrinsic pathway