RADIOLYSIS, PHOTOLYSIS AND SONOLYSIS OF CELLS AND THEIR CONSTITUENTS

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Summary of work: Sonodynamic therapy is a promising new modality for cancer treatment based on the synergistic effect on cell killing by the combination of a drug (a sonosensitizer; usually a porphyrin) and ultrasound. The effectiveness of sonodynamic therapy has been demonstrated in cell studies and in tumor-bearing animals.The mechanism of this drug-dependent sonosensitization is unknown, but it seems likely that different mechanisms of sonosensitization operated for different classes of sonosensitizers. As part of a program to elucidate these mechanisms, we investigated the free radicals and the hydrogen peroxide produced during ultrasound exposure of typical cell culture medium ( RPM-1640 ) using electron paramagnetic resonance ( EPR) and spin-trapping techniques. Free radicals and/or hydrogen peroxide produced by exposure of cells to ultrasound are potentially cytotoxic and mutagenic. The formation and type of free radicals can be substantially modulated by the chemical composition of the media in which the ultrasound exposures of cells are carried out. In the current study, we examined the free radical intermediates formed during the ultrasound exposure of a typical cell culture medium (RPMI-1640); the dominant free radicals that were identified by spin-trapping were derived from the hydrophobic amino acids Trp, Leu, and Phe, and were formed by hydrogen abstraction from these amino acids. Compared to exposures in phosphate-buffered saline, the yield of OH radicals and H2O2was significantly reduced in the cell cultrure medium, glucose (the main organic component of the medium) and the hydrophobic amino acids (Trp, Phe, Tyr, Val, Met ) being chiefly responsible for this effect . In contrast, the other non-hydrophobic amino acids, did not contribute significantly to the . OH or H2O2 decrease. These findings are consistent with the accumulation of hydrophobic solutes at the liquid- gas interface of collapsing cavitation bubbles resulting in increased efficiency of radical scavenging.Recent Publications:Kondo,T.,Misik,V.and Riesz,P. Free Rad Biol Med 1998;25:605-12Misik,V. and Riesz,P. Free Rad Biol Med 1999;26:936- 43Misik,V., Miyoshi,N. and Riesz,P. Free Rad Biol Med 1999;26:961- 67Misik,V. and Riesz,P. in Sonochemistry and Sonoluminescenceed.L.A.Crum et al. (eds.) NATO ASI Series,Kluwer Academic Publishers, 225-236, 1999 - cancer, electron paramagnetic resonance (EPR), sonochemistry, sonodynamic therapy, spin trapping, ultrasound,