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

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Abstract
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.