TET-mediated DNA demethylation plays an important role in arsenic-induced HBE cells oxidative stress via regulating promoter methylation of OGG1 and GSTP1.

Environmental exposure to arsenic remains a worldwide public health challenge. Oxidative stress and aberrant DNA methylation are both characteristics of arsenic toxicology; however, the relationship between these is not well understood. Ten-eleven translocation (TET1, TET2 and TET3), which is the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), plays a central role in the DNA demethylation process. Further, it can prevent cytosine-phosphate-guanine (CpG) islands from developing abnormal hypermethylation under oxidative stress. Here, we observed that NaAsO could induce oxidative stress in human bronchial epithelial (HBE) cells. This was accompanied by an inhibition of TET-mediated DNA demethylation. Subsequent results showed that TET1 and TET2 siRNA led to further inhibition of genome 5hmC and a higher level of oxidative stress in NaAsO-treated HBE cells. Conversely, l-ascorbic acid enhanced TET proteins and effectively upregulated 5hmC, which antagonized the NaAsO-induced oxidative stress. Additionally, the TETs positively regulated the promoter methylation of the antioxidant genes 8-oxoguanine DNA glycosylase (OGG1) and glutathione S-transferase Pi 1 (GSTP1). Taken together, the results indicate that arsenic induced the inhibition of TET-mediated DNA demethylation, which induced promoter hypermethylation, inhibiting the expression of the OGG1 and GSTP1, and increasing oxidative stress in lung cells in vitro. l-ascorbic acid effectively alleviated arsenic-induced oxidative stress by restoring TET function.