ANTIMUTAGENIC AND PROMUTAGENIC ACTIVITY OF ASCORBIC-ACID DURING OXIDATIVE STRESS

Ascorbic acid (AA) has both antioxidant and prooxidant activities. How ever, there have not been any studies to elucidate the molecular mecha nisms that determine whether AA functions as an anti- or a prooxidant during oxidative stress. The results of this study, using the Chinese hamster ovary cell line AS52 as a model system, demonstrate that there is a temporal relationship between the anti-and prooxidant activities of a physiologically relevant concentration of AA (50 mu M) and oxida tive stress. Treatment of cells with AA (50 mu M) 24 hr prior to treat ment of the cells with a radical generating system (RGS) results in a statistically significant inhibition of the cytotoxicity and mutagenic ity associated with exposure of AS52 cells to oxidative stress. Conver sely, cotreatment of cells with AA and the RGS results in a statistica lly significant increase in both the cytotoxic and mutagenic effects o f oxidative stress when compared to cell populations exposed only to t he RGS. The results, using a novel histochemical-computer image analys is system to detect hydrogen peroxide (H2O2), also demonstrate that th ere is a direct correlation between the ability of AA to decrease the levels of H2O2 in cells and the cytotoxic and mutagenic effects of oxi dative stress. This study suggests that the time at which AA is admini stered in relation to exposure to oxidative stress has an impact on AA antimutagenic activity, and this may explain the conflicting results concerning the effectiveness of AA as a cancer chemopreventive agent. (C) 1997 Wiley-Liss, Inc.