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Keywords:

  • DNA repair;
  • HBEC;
  • NO and its derivative;
  • oxidative stress;
  • p-ATM

Abstract

Ozone may lead to DNA breaks in airway epithelial cells. p-ATM (phosphorylated ataxia telangiectasia mutated) plays a pivotal role in DNA repair. Derivatives of NO (nitric oxide) are regulators of the phosphorylation, and NO is increased under oxidative stress. The present study was aimed to study the effect of NO donor l-arg (l-arginine) on DNA damage repair in human bronchial epithelial cells exposed to ozone and the potential mechanisms involved. HBECs (human bronchial epithelial cells) were cultured with or without ozone (1.5 ppm, 30 min), DNA breaks were measured with a comet assay and agarose gel electrophoresis, cell cycling was determined by flow cytometry and p-ATM was measured by immunofluorescence and Western blot. Data were analysed by ANOVA (analysis of variance). P<0.05 was considered as significant. Ozone induced marked DNA breaks, G1-phase arrest and increased expression of p-ATM in HBECs, while wortmannin reduced the levels of p-ATM induced by ozone; the NO donor, l-arg, minimized the effects of ozone-induced DNA breaks and increased the level of p-ATM, while the NO synthase inhibitor, l-NMMA [N(G)-minomethyl-l-arginine], restrained those effects of l-arg. The effect of l-arg on DNA repair is NO-mediated, and p-ATM is implicated in the processes of DNA repair.