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