The effect of hyperthermia on the uptake and cytotoxicity of melphalan in Chinese hamster ovary cells.

The effect of temperature on the cytotoxicity of melphalan in CHO cells was studied in an in vitro clonogenic assay. The cytotoxicity of melphalan was significantly increased at elevated temperatures with a 4 fold increase in cytotoxicity at 42 degrees C compared to 37 degrees C. The effect of temperature on membrane permeability to melphalan was studied to determine whether the increase in cytotoxicity was due to increased intracellular drug levels. Melphalan influx and efflux rates both increase with increasing temperature. There is, however, a small net increase in steady state intracellular drug levels with increasing temperature with a 20% increase in intracellular drug levels at 42 degrees C compared to 37 degrees C. The increase in drug uptake observed in insufficient to explain the much greater increase in cytotoxicity with increasing temperature.