Growth delay in small EMT6 spheroids induced by cytotoxic drugs and its modification by misonidazole pretreatment under hypoxic conditions.

Experiments have been carried out to determine whether the growth delay induced in small EMT6 spheroids (approximately 250 micrometers in diameter) by a range of cytotoxic drugs can be increased by pre-incubation of the spheroids under hypoxic conditions with misonidazole (MISO). Hypoxic pre-incubation was for 3 or 5 h in the presence of 5 mM MISO, and caused a growth delay of about 1 day or 2 days respectively. Sensitization to nitrogen mustard (HN2), melphalan, chlorambucil, BCNU and CCNU was seen, but the shapes of the dose-response curves and the ratio of effects for 3 h and 5 h pretreatment varied between the drugs. In contrast to the other agents, hypoxic pre-incubation with MISO reduced the spheroid response to adriamycin.