5688

Oxidative stress, or the production of oxygen-centered free radicals, has been hypothesized as the major source of DNA damage that can lead to a variety of diseases including cancer. It is known that 8-hydroxy deoxyguanosine (8-oxo-dG) is an useful biomarker of oxidative DNA damage. Our recent data showed that JWA, initially being cloned as a novel cell differentiation associate gene, was also actively responsive to environmental stressors, such as heat shock and oxidative stress.We applied modified comet assay and bacterial repair endonucleases system (endonuclease III, foramidopyrimidine glycosylase) to investigate if JWA was involved in hydrogen peroxide (H2O2) induced DNA damage and repair in K562 and MCF-7 cells, and to confirm if the damage was 8-oxo-dG modified. The comet assay showed that the tail length and percentage of DNA in tail were greatly increased after addition of repair endonucleases. JWA gene was found actively regulated by H2O2 and its expression was induced in K562 and MCF-7 cells. Based on these results, we suggested that the H2O2 induced 8-oxo-dG formation was dose-dependent in K562 and MCF-7 cells. Furthermore, JWA may actively participate in the signal pathways of oxidative stress and enhance intracellular defenses to compensate H2O2-induced oxidative stress.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]