Levels of reactive oxygen species and primary antioxidant enzymes in WI38 versus transformed WI38 cells following bleomcyin treatment.

Bleomycin (BLM) is an anticancer drug that generates reactive oxygen species (ROS) after interacting with iron and oxygen. We hypothesized that BLM could cause a different status of oxidative stress in normal versus tumor cells due to possible altered redox status and gene expression in cells following transformation. In this study, the extent of cytotoxicity, levels of ROS, and activities of antioxidant enzymes were compared between normal WI38 cells and SV40-transformed WI38 (VA13) cells following BLM treatment. Basal activities of MnSOD and catalase were lower in VA13 cells and basal ROS levels were higher in VA13 cells. Although BLM caused greater growth inhibition and apoptosis in VA13 cells, it increased ROS levels at an earlier time point in WI38 cells. Moreover, BLM treatment (100 microg/ml) had no effect on the activities of MnSOD, CuZnSOD, and catalase, but increased the activities of glutathione peroxidase (GPX) in WI38 cells after a 48-h treatment and in VA13 cells after a 24- and 48-h treatment. Northern blot analysis indicated that the increase in GPX activities was due to increased transcript levels of GPX1 but not GPX4 in both cells. Our results indicate selective induction of the GPX1 gene by BLM and different redox responses to BLM between WI38 and VA13 cells.