Abstract
Widespread application of titanium dioxide nanoparticles (nTiO(2)) and ubiquitous cadmium (Cd) pollution may increase their chance of co-existence in the natural environment. Toxicological information on co-exposure of nTiO(2) and Cd in mammalian models is largely lacking. Hence, we studied the combined effects of nTiO(2) and Cd in human liver (HepG2) and breast cancer (MCF-7) cells. We observed that nTiO(2) did not produce toxicity to HepG2 and MCF-7 cells. However, moderate concentration of Cd exposure caused cytotoxicity to both cells. Interestingly, non-cytotoxic concentration of nTiO(2) effectively enhanced the oxidative stress response of Cd indicated by pro-oxidants generation (reactive oxygen species, hydrogen peroxide, and lipid peroxidation) and antioxidants depletion (glutathione level and glutathione reductase, superoxide dismutase, and catalase enzymes). Moreover, nTiO(2) potentiated the Cd-induced apoptosis in both cells suggested by altered expression of p53, bax, and bcl-2 genes along with low mitochondrial membrane potential. Cellular uptake results demonstrated that nTiO(2) facilitates the internalization of Cd into the cells. Overall, this study demonstrated that non-cytotoxic concentration of nTiO(2) enhanced the toxicological potential of Cd in human cells. Therefore, more attention should be paid on the combine effects of nTiO(2) and Cd on human health.