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Ultrasound Enhanced Drug Toxicity on Chinese Hamster Ovary Cells in Vitro¹

Department of Radiation Oncology, Stanford University Medical Center, Stanford, California 94305

Chinese hamster ovary cells (HA1) were exposed to therapeutic ultrasound (F = 2.025 MHz) in the presence of various drugs at temperatures of 37–43°C. The space averaged intensities used were 0.5–2 W/cm². The survival of these cells was subsequently tested using the clonogenic assay. Marked enhancement by ultrasound of the cytotoxicity of Adriamycin and amphotericin B was observed. For Adriamycin, the potentiation was dependent upon the intensity of sonication (exposure duration being 30 min). At 0.5 W/cm², there was enhancement of cytotoxicity above 41°C. At 1 W/cm², there was a 3-order increase in cytotoxicity at 37°C. Thus an increase in intensity resulted in a decrease in "threshold" temperature. The effect with Adriamycin could be explained in part by an increase in net uptake of drug into the cells. Further, ultrasound was observed to increase the sensitivity of cells to Adriamycin. For amphotericin B, the enhancement was observed only at exposure durations >30 min and at 43°C. There was no enhancement observed for cisplatin and etoposide. From these results, it appears that ultrasound potentiates the cytotoxicity of drugs the mode of action of which (at least in part) involves the plasma membrane.

¹ This work was supported by National Cancer Institute Grant No. CA 19386.

Received 9/19/88. Revised 4/ 3/89. Accepted 8/ 3/89.

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