Cadmium (Cd) and copper (Cu) are widely present in foods. However, their adverse effects on human gastric epithelium are not fully understood. Here, human gastric epithelial cells (SGC-7901) were employed to study the toxicity and associated mechanisms of Cd+Cu co-exposure. Their effects on cell viability, morphology, oxidative damage, cell cycle, apoptosis, and the mRNA levels of antioxidases and cell cycle regulatory genes were investigated. Co-exposure to Cd (5 μM)/Cu (10 μM) induced >40% cell viability loss, whereas little effect on cell viability at <10 μM Cd or 40 μM Cu. Compared to individual exposure, co-exposure induced greater oxidative damage by elevating ROS (3.5 folds), malondialdehyde (2.3 folds) and expression of SOD1 and HO-1 besides inhibiting CAT, GPX1 and Nrf2. A marked S cell-cycle arrest was observed in co-exposure, evidenced by more cells staying in the S phase (36%), up-regulation of cyclins-dependent kinase (CDK4) and CDKs inhibitor (p21) and down-regulation of CDK2, CDK6 and p27. Furthermore, higher apoptosis (22%) with floated and round cells occurred in co-exposure group. Our data implicate the cytotoxicity of Cd+Cu co-exposure was higher than individual exposure, and individual assessment would underestimate their potential health risk. Oxidative stress and cell cycle arrest possibly played a role in Cd+Cu induced toxicity and apoptosis in SGC-7901 cells. Our data suggest the importance to reduce Cd in foods to decrease its adverse impacts on human digestive system.

食物中广泛存在镉（Cd）和铜（Cu）。然而，它们对人胃上皮的不利影响尚未完全了解。在这里，人类胃上皮细胞（SGC-7901）被用来研究Cd + Cu共暴露的毒性和相关机制。研究了它们对细胞活力，形态，氧化损伤，细胞周期，细胞凋亡以及抗氧化酶和细胞周期调控基因mRNA水平的影响。共同暴露于Cd（5μM）/ Cu（10μM）会引起> 40％的细胞活力损失，而对<10μMCd或40μMCu的细胞活力几乎没有影响。与单独暴露相比，共同暴露通过升高ROS（3.5倍），丙二醛（2.3倍）以及SOD1和HO-1的表达，除了抑制CAT外，还引起更大的氧化损伤，GPX1和Nrf2。在共同暴露中观察到明显的S细胞周期停滞，表现为更多的细胞停留在S期（36％），细胞周期蛋白依赖性激酶（CDK4）和CDKs抑制剂（p21）的上调。CDK2，CDK6和p27。此外，共同暴露组的漂浮细胞和圆形细胞的凋亡率更高（22％）。我们的数据表明，Cd + Cu共同暴露的细胞毒性高于个人暴露，个人评估会低估其潜在的健康风险。氧化应激和细胞周期阻滞可能在Cd + Cu诱导的SGC-7901细胞毒性和细胞凋亡中起作用。我们的数据表明减少食品中Cd的重要性，以减少其对人体消化系统的不利影响。