Panel A. MMC undergoes a one electron reduction to form a semiquinone free radical intermediate during redox cycling. In the presence of molecular oxygen, the radical disproportionates to form superoxide anion and the parent compound. Modified from Bachur et al. (8). Panel B. Comparison of the cytotoxicity of MMC under aerobic and hypoxic conditions in CHO cells. CHO-WT cells and CHO-OR cells were seeded into 6- or 24-well culture plates (2.5 × 104 cells/well or 5,000 cells/well) and allowed to adhere overnight. The medium was then replaced with growth medium supplemented with increasing concentrations of MMC and cultured either 3 h (left panels, 3 h exposure to MMC) or 24 h (right panels, 4 d exposure to MMC) under aerobic or hypoxic conditions as described in the Materials and Methods. Cell growth was assayed after an additional 3 d in culture by counting cells using a Coulter Counter. Each point represents a mean ± SEM (n = 3). Panel C. Cytotoxicity of menadione under aerobic and hypoxic conditions in CHO cells. * p<0.05, *** p<0.001.