Mechanisms of Cd and Cu induced toxicity in human gastric epithelial cells: Oxidative stress, cell cycle arrest and apoptosis

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 mu M)/Cu (10 mu M) induced >40% cell viability loss, whereas little effect on cell viability at <10 mu M Cd or 40 mu M 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 1I0-1 besides inhibiting CAT, GPX1 and Ntf2. 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 coexposure 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. Published by Elsevier B.V.

Automated summary

The study found that co-exposure to Cd and Cu has a greater toxicity on human gastric epithelial cells, mainly through oxidative stress and cell cycle arrest leading to cell damage and apoptosis.