IN-VITRO MECHANISMS OF CHEMOPOTENTIATION BY TONE-BURST ULTRASOUND

We investigated in vitro enhancement of cytotoxicity of chemotherapeut ic agents by tone-burst ultrasound. Survival of CHO cells exposed to c hemotherapeutic agents in culture medium was determined with and witho ut insonation (1.62 and 0.29 MHz, 10% duty cycle). Insonations up to 0 .4 MPa peak pressure (5 kW/m(2) spatial and temporal average) occurred in the middle of 1 h drug exposures. Cytotoxicity in ultrasound contr ol groups was never observed. Ultrasound increased the clonogenic cyto toxicity of adriamycin (p = 0.00027 by paired t test) and diaziquone b ut not of cisplatin or mitomycin C. Potentiation of adriamycin depende d on exposure time and tone-burst frequency. (OH)-O-. production in wa ter occurred at intensities as low as 0.4 kW/m(2), but did not increas e with added adriamycin. Ultrasound did not affect membrane fluidity, but moderately increased cellular adriamycin accumulation, possibly ex plaining the observed drug potentiation.