Effects of Hypochlorous Acid on Oxidative DNA Damage in HumanAlveolar Epithelial Cells

Abstract

Activated neutrophils generate hypochlorous acid (HOCl) via the release of the enzyme myeloperoxidase and hydrogenperoxide (H2O2). There is accumulating evidence indicating an association between inflammation and carcinogenesis.However, the underlying mechanisms are largely unknown. In the present study, we found that HOCl induced a slightincrease in 8-OHdG DNA lesions, but did not lead to significant DNA strand breakage in human alveolar epithelialcells. In addition, exposure of HOCl to A549 cells did not induce a significant increase in the level of p21 and GADD45genes. In contrast, H2O2, the well-known DNA damaging agent and precursor of HOCl, significantly induced oxidativeDNA damage and increased the level of p21 and GADD45 gene expression. Together these results suggest that mutageniceffects of HOCl in human alveolar epithelial cells are unlikely explained by the ability of HOCl to induce the formationof pre-mutagenic 8-OHdG DNA lesions and DNA strand breaks.