Induced resistance in cells exposed to repeated low doses of H2O2 involves enhanced activity of antioxidant enzymes

We have derived cells from the Chinese hamster V79 cell line by conditioning them with repeated low doses of hydrogen peroxide (H2O2). This mimics the physiological condition where cells are repeatedly exposed to low levels of oxidants. In an attempt to characterize such cells, we have exposed both conditioned cells (V79C) and the parental V79 cells (V79P) to different types of cytotoxic agents and compared their sensitivity to cell killing. The V79C cells were found to be stably resistant to killing by agents that produced toxicity through oxidative stress, e.g. H2O2 and cisplatin. It was also found that the lipid peroxidation produced by these agents were considerably lower in the V79C cells. Thus, the difference in sensitivity could be due to lesser extent of damage to these cells. V79C cells had greater antioxidant defense through higher GSH content and greater activity of enzymes such as Cu-Zn superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), which provided protection from damage. Enzyme activities were also assayed at different times after treatment with various cytotoxic agents; there was a relatively large increase in SOD activity which perhaps plays a key role in determining the resistance of the V79C cells to killing.