The effect of exposure to elevated temperatures on membrane permeability to adriamycin in Chinese hamster ovary cells in vitro.

The effect of environmental temperature on plasma membrane permeability to Adriamycin was studied in Chinese hamster ovary (CHO) cells in vitro using flow cytometry. Initial rates of uptake increased steadily between 23 degrees C and 47 degrees C and there was a greater than 2-fold increase in permeability between 37 degrees C and 47 degrees C. The increase in permeability with increasing temperature was greater than expected based on the model of passive drug influx. Adriamycin uptake was also measured at 37 degrees C following previous exposure of the cells to elevated temperatures. Twenty-minute preexposures to temperatures above 41 degrees C caused a significant decrease in membrane permeability, which fell to approximately 60% of control levels after exposure to 45 degrees C. Longer periods of pre-exposure to temperatures as low as 40 degrees C were also shown to decrease membrane permeability to Adriamycin subsequently measured at 37 degrees C. The state of decreased permeability to Adriamycin induced by hyperthermia persisted for at least 2 h. The thermally induced decrease in membrane permeability to Adriamycin is of potential importance to the design of optimal schedules for thermochemotherapy.