Effect of temperature on the cytotoxicity of vindesine, amsacrine, and mitoxantrone.

The effect of elevated temperature on the cytotoxicity of three new anticancer drugs (vindesine, mitoxantrone, and amsacrine [AMSA]) was tested in Chinese hamster ovary cells in vitro. Three distinct patterns of interaction with hyperthermia were observed. Vindesine, tested at 37 degrees C, produced a 50% cell kill when concentrations of greater than or equal to 1.0 micrograms/ml (up to 3.0 micrograms/ml) for 1 hour were used. At 42.4 degrees C, concentrations greater than 1.0 micrograms/ml for 1 hour caused a 60% cell kill (an additive cytotoxic effect). Mitoxantrone produced concentration-dependent lethality at 37 degrees C (89% cell kill after 0.25 micrograms/ml for 1 hour; 99% cell kill after 1.0 micrograms/ml for 1 hour). Exposure to mitoxantrone at 42.4 degrees C resulted in synergistic cytotoxicity (97% cell kill after 0.25 micrograms/ml for 1 hour; 99.98% cell kill after 1.0 micrograms/ml for 1 hour). In contrast, treatment with AMSA at 42.4 degrees C inhibited cytotoxicity (99.98% cell kill after 5 micrograms/ml for 1 hour at 37 degrees C; 91% cell kill after 5 micrograms/ml for 1 hour at 42.4 degrees C). AMSA was not inactivated after being heated at 42.4 degrees C for 1 hour prior to treatment of cells at 37 degrees C.