MECHANISM OF ULTRASOUND ENHANCED PORPHYRIN CYTOTOXICITY .1. A SEARCH FOR FREE-RADICAL EFFECTS

Intense ultrasound beams may have the potential to treat malignant tum ours when combined with sensitizers, often called sonodynamic agents. Some of these agents, e.g., the porphyrins, are currently used for pho todynamic therapy. However, the experimental evidence for ultrasound a ctivation of sensitizers is inconsistent. This paper attempts to disco ver whether the :yield of free radicals such as . OH and . H, which ar e produced by transient cavitation, could explain the killing of Chine se hamster ovary (CHO) cells in vitro with and without sonodynamic age nts. CHO cells were irradiated with ultrasound beams in phosphate-buff ered saline or in growth medium, and the immediate cell lysis and loss of cell colony forming ability were measured. Under our specific cond itions, in which the standing wave patterns were minimized, a general correlation was observed between the transient cavitation, free radica l production, and cytotoxicity. However, the yield of free radicals wa s much too small to explain the cell killing observed. We conclude tha t cytotoxicity is not linked to attack from free radicals formed outsi de the cells. In our experiments, immediate cell lysis is closely link ed to the transient cavitation, which is known to produce shear forces that disrupt cellular membranes. We hypothesize that the loss of cell colony forming ability is also linked to damage of cellular membranes . (C) 1997 World Federation for Ultrasound in Medicine & Biology.