Olaquindox induces DNA damage via the lysosomal and mitochondrial pathway involving ROS production and p53 activation in HEK293 cells

- Olaquindox exerts genotoxic effects on HEK-293 cells.
- Lysosomal leakage is likely to be an important event of olaquindox-induced DNA damage.
- Olaquindox-induced DNA strand breaks could be mediated by oxidative stress.

Olaquindox (OLA) is a potent antibacterial agent used as a feed additive and growth promoter. In this study, the genotoxic potential of OLA was investigated in the human embryonic kidney cell line 293 (HEK293). Results showed that OLA caused significant increases of DNA migration. Lysosomal membrane permeability and mitochondrial membrane potential were reduced after treatment with OLA. OLA was shown to induce ROS production and GSH depletion. The expression of p53 protein is increased in cells incubated with OLA. The activation of p53 and ATM gene was assessed by exposure to OLA. Furthermore, NAC reduced DNA migration, ROS formation, GSH depletion and the expression of the p53 protein and gene. And desipramine significantly decreased AO fluorescence intensity and the expression of the p53 protein and gene. These results support the assumption that OLA exerted genotoxic effects and induced DNA strand breaks in HEK293 cells, possibly through lysosomal-mitochondrial pathway involving ROS production and p53 activation.