In vitro mechanisms of chemopotentiation by tone-burst ultrasound

We investigated in vitro enhancement of cytotoxicity of chemotherapeutic agents by tone-burst ultrasound. Survival of CHO cell exposed to chemotherapeutic agents in culture medium was determined with and without insonation (1.62 and 0.29 MHz, 10% duty cycle). Insonations up to 0.4 MPa peak pressure (5 kW/m2 spatial and temporal average) occurred in the middle of 1 h drug exposures. Cytotoxicity in ultrasound control groups was never observed. Ultrasound increased the clonogenic cytotoxicity of adriamycin (p = 0.00027 by paired t test) and diaziquone but not of cisplatin or mitomycin C. Potentiation of adriamycin depended on exposure time and tone-burst frequency. .OH production in water occurred at intensities as low as 0.4 kW/m2, but did not increase with added adriamycin. Ultrasound did not affect membrane fluidity, but moderately increased cellular adriamycin accumulation, possibly explaining the observed drug potentiation.