Effect of prolonged exposure of HELA S3 cells to low concentrations of misonidazole.

The cytotoxic and radiosensitizing effects of low concentrations of misonidazole were examined by measurement of the colony-forming ability and growth of HeLa S3 cells. Under hypoxic conditions, cytotoxicity depended on the misonidazole concentration and the exposure time. After 24 hr exposure, the surviving fraction of cells treated with 0.1 mM misonidazole decreased to 0.2. The ability of cells to adhere to the growth surface of plastic dishes was reduced by 0.1 mM misonidazole upon 24 hr hypoxia and this effect persisted even during subsequent euoxia, irrespective of whether the drug was removed from the original growth medium. The growth of aerobic cells was not affected when 0.1 mM misonidazole containing medium, obtained from the hypoxia-treated dishes, was applied, nor when those cells were exposed for 72 hr to freshly prepared 1.0 mM misonidazole. Upon 24 hr exposure, 0.1 mM misonidazole exerted no obvious radiosensitizing effect on hypoxic cells. Based on these results, it is suggested that continuous administration of low doses of misonidazole may be efficacious as a specific chemotherapeutic in the treatment of hypoxic cells in tumor tissue.