ASA 125th Meeting Ottawa 1993 May

3aPA9. An investigation of mechanisms for drug-mediated cell damage using acoustic cavitation.

R. J. Jeffers

R. Q. Feng

J. B. Fowlkes

Dept. of Radiol., Univ. of Michigan, Ann Arbor, MI 48109-0553

J. W. Hunt

University of Toronto, Toronto, ON, Canada

C. A. Cain

Univ. of Michigan, Ann Arbor, MI 48109

Several different research groups including this one have demonstrated that the application of ultrasound in the presence of certain anticancer agents will increase the in vitro and in vivo cytotoxicity of the drug significantly beyond the strictly additive effect of ultrasound alone. Recent in vitro experiments indicate that the addition of cavitation nuclei in the form of albumin-stabilized microbubbles can greatly enhance the cell killing potential of the combination treatment on HL-60 human promyelocytic leukemia cells. Several measurement techniques currently in use will be described for correlating cytotoxicity with cavitation activity in order to investigate the mechanism for cell damage. One of the more promising methods thus far has been time-integrated subharmonic emission versus cell lysis where the latter is measured by the amount of extracellular lactate dehydrogenase. The use of the subharmonic to indicate the amount and severity of cavitation accommodates variations in cavitation threshold and consistency of cavitation nuclei. [Work supported by USPHS Grant No. CA-55357.]