Exposure to lead (Pb) continues to be a significant worldwide problem. Pb is a highly poisonous heavy metal affecting several organ systems in the body. Although Pb has been shown to be genotoxic to experimental animals and humans, the underlying mechanisms are still not understood. An indirect mechanism related to the inhibition of DNA repair systems by Pb has been suggested. Heavy metals can interfere with the activities of several proteins and gene expressions. Recent studies gathered in this review article demonstrated an altered expression of DNA repair genes due to Pb toxicity. However, their findings are conflicting. Furthermore, the interaction of Pb and epigenetic mechanisms regulating gene expression may have a crucial role in the inhibition of DNA repair systems. Therefore, additional studies are needed to evaluate these findings and to obtain a complete picture of the genotoxic properties of Pb and the underlying mechanisms that may have a crucial role in carcinogenesis.

Exposure to lead (Pb) continues to be a significant worldwide problem. Pb is a highly toxic heavy metal affecting several organ systems in the body. There has been reported to have potential genotoxic properties to various cells. However, the underlying mechanisms of lead-induced toxicity are still unknown. The present study aimed to investigate the lead-induced cytotoxicity in human renal proximal tubular epithelial cells and its underlying DNA damage mechanisms. Lead exposure caused DNA damage as demonstrated by increased 8-OHdG/dG ratio in cells even at a relatively normal dose (10μg/dL). Lead also led to producing oxidative stress as characterized by increased intensity of the Reactive Oxygen Species (ROS) indicator. ROS overproduction should be the reason for lead-induced DNA damage. Therefore, the effects of Lead on ROS elimination should be the main reason for lead-induced oxidative stress in human renal proximal tubular epithelial cells. After lead acetate (PbAc) treatment, the cell viability significantly decreased in a dose-dependent manner, and the accumulation of cellular ROS was observed. 8-OHdG levels, a marker of oxidative DNA damage, were significantly increased by both acute and chronic Pb exposure. Interestingly, the mRNA expression of the 8-oxoguanine DNA glycosylase 1 (hOGG1) significantly decreased after acute and chronic exposure. In conclusion, our study provides the first evidence to demonstrate that acute and chronic Pb exposure results in the altered expression of DNA glycosylases genes indicating the impairment of DNA repair pathways and contributing to DNA damage. These findings should be useful for the more comprehensive assessment of the toxic effects of Pb.