Hypoxia and acidity increase the cytotoxicity of mitomycin C and carboquone to human tumor cells in vitro.

To clarify the influence of hypoxic and acidic environments on the cytotoxicity of mitomycin C (MMC) and carboquone (CQ), the cytotoxicity was assessed based on decreases in intracellular ATP levels of HeLa cells exposed to the drugs at various acidic pH (pH 5.8-6.8) and low oxygen tension (5% and 0% O2) in vitro. Hypoxia and acidity individually increased the cytotoxicity of MMC, although hypoxia no longer increased it under acidic conditions. On the other hand, the cytotoxicity of CQ was enhanced in the presence of hypoxic and acidic conditions, and even more so with their combination. We conclude that acidity is a determining factor and excels hypoxia in influencing the cytotoxicity of MMC and that these two factors act synergistically on CQ.