Effects of oxygen on the antioxidant responses of normal and transformed cells

Basal antioxidant defense levels are often aberrant in tumor cells; however, less attention has been given to differences in the way that normal and transformed cells respond to changes in oxidative stress. This study evaluated differences in the responses of various normal and transformed cell lines to different oxygen tensions. Exposure to hyperoxia generally failed to induce either the activity of GSH peroxidase (GPx) or the manganese-containing form of superoxide dismutase (MnSOD) after 48 h, although at 605 mm Hg oxygen, small inductions of MnSOD activity were observed in adult lung fibroblasts and amelanotic melanoma. Exposure to 605 mm Hg O2 for 48 h was inhibitory to GPx activity. MnSOD activity was strongly induced in virally transformed WI-38 cells by treatment with the herbicide paraquat or inhibition of GSH synthesis with BSO. In normal cells GSH concentration was proportional to ambient oxygen tension. Tumor cells exhibited greater GSH concentrations at low oxygen tensions than normal cells but were unable to increase GSH in response to elevation of oxygen tension. These results reveal differences in tumor and normal cell responses to changes in ambient oxygen tension and show that MnSOD activity is inducible when an appropriate stimulus is applied.