Abstract
The effect of hypoxic misonidazole (MISO) pretreatment on the subsequent heat sensitivity of EMT6 multicellular tumour spheroids has been investigated. Spheroids were grown in static culture and treated when either 200-300 micrometers or 650-800 micrometers in diameter. Pretreatment was carried out in glass spinner vessels containing 100 ml medium with or without 5mM MISO under conditions of hypoxia. Three-hour hypoxic pretreatment with 5mM MISO significantly enhanced the subsequent response of 200 micrometers spheroids to heat at 43 degrees C. Oxic incubation at 37 degrees C between pretreatment and heating caused progressively loss of heat sensitization with time, recovery being almost complete after 6 h. Recovery was inhibited by incubation at 0 degree C during the interval. Preheating 200 micrometers spheroids at 43 degrees C for 2 h increased their subsequent sensitivity to hypoxic MISO at 37 degrees C. These results are discussed in relation to known mechanisms of MISO metabolism.
Highlights
In spinner culture have been shown to be In this paper we have further investigamore sensitive to radiation, hyperthermia ted the development of heat sensitization at 44 5°C and some chemotherapeutic after MISO treatment using EMT6 agents
Toxicity has been reported in vivo with the combination of MISO with cyclophosphamide, melphalan, BCNU, MATERIALS AND METHODS
In this paper we have clearly demonstrated that a 3h exposure to 5mM MISO
Summary
A 3h hypoxic exposure alone had no significant effect either on cell survival or on the heatresponse curve at 43°C (data not shown). It can be seen that the increased heat sensitivity after MISO treatment, as demonstrated by the cell-survival data, is reflected in the regrowth data for this experiment.
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