The Response of EMT6 Tumor Spheroids to Combined Treatment with Misonidazole and Either Nitrogen Mustard, Adriamycin, or BCNU

Experiments have been carried out to determine whether pretreatment of multicellular spheroids with misonidazole (5 mM) for 21 hours can remove a population of cells which are resistant to conventional chemotherapy. The experiments were based on the notion that misonidazole is selectively cytotoxic to the innermost, hypoxic cells of spheroids. The spheroids used were of the EMT6/Ca/VJAC line and the drugs studied were nitrogen mustard (HN2), Adriamycin, and BCNU. Treatment with sensitizer alone reduced the survival of clonogenic cells in large (650-800 microns in diameter) spheroids to around 35% of control. This surviving 35% were found to be no more sensitive to Adriamycin and BCNU than the total clonogenic population in previously untreated spheroids. In experiments with nitrogen mustard, the population surviving sensitizer treatment appeared to be more resistant than the total population.