Effect of hyperthermia on the sensitivity of human colon carcinoma cells to mitoxantrone.

The effect of temperature on the cytotoxicity of mitoxantrone (MX) was investigated by exposing human WIDR colon carcinoma cells to elevated temperatures in the presence of drug. The survival of treated cells was determined by their ability to proliferate and to form colonies in vitro. It was demonstrated that incubation of WIDR cells with MX at 42 degrees C produced not only a higher toxicity but also a more rapid action than when cells were exposed to drug at 37 degrees C. By measuring the amounts of 3H-MX incorporated by treated tumor cells, it was shown that cells at 42 degrees C induced an approximately threefold increase in drug uptake when compared to cells at 37 degrees C. The effect seemed long-lasting but preheating did not induce tolerance to a subsequent exposure to MX hyperthermia. Therefore, it is clear that the cytotoxic potency of MX can be augmented by elevated temperature possibly by enhancing the uptake of drug. The present findings may prove useful for designing an effective clinical regimen of MX thermochemotherapy.