In Vitro Pre-incubation with Misonidazole Under Hypoxic Conditions--effect on Drug Response of EMT6 Spheroids

We have studied the effect of pretreating small (approximately 250 mu diameter) EMT6 spheroids with 5mM misonidazole under hypoxic conditions upon their subsequent response to a number of cytotoxic drugs. Growth delay assay was used to quantify spheroid response. The pretreatment time was either 3 or 5 hours. Such pretreatment produced an increase in spheroid response to nitrogen mustard, melphalan, chlorambucil, BCNU and CCNU but a reduction in the response to adriamycin. The relative effects of 3 hr and 5 hr pretreatment varied among the drugs. In the case of melphalan and CCNU we have shown that the increased growth delay is not caused by any inhibition of recovery from potentially lethal drug damage.