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 effects of cell killing by a combination of sonosensitzer and ultrasound. Ultrasound can penetrate deeply into tissue and can be focused in a small region of tumor to activate non-toxic molecules (e.g. porphyrins ) thus minimizing undesirable side effects. The experimental evidence suggests that sonosensitization is due to the chemical activation of sonosensitizers inside or in close vicinity of hot collapsing cavitation bubbles to form sensitizer-derived radicals either by direct pyrolysis of the sensitizer at the water-gas interface or due to the reactions of hydrogen atoms and hydroxyl radicals formed by the pyrolysis of water. The free radicals derived from the sonosensitizer (mostly carbon-centered) react with oxygen to form peroxyl and alkoxyl radicals. Unlike OH radicals and H atoms which are formed by pyrolysis inside cavitation bubbles, the reactivity of alkoxyl and peroxyl radicals with organic compounds in biological media is much lower and hence they have a higher probability of reaching critical cellular sites. Recently we have succeeded in spin-trapping the carbon radicals formed during the sonolysis of aqueous solutions of various porphyrins .Umemura et al have proposed that the sonoluminescent light produced during cavitational collapse of microbubbles is responsible for the photoexcitation of the sensitizer, with subsequent formation of singlet oxygen, a known reactive cytotoxic species. We recently obtained further evidence against the singlet oxygen mechanism of Umemura by studying the sonolysis of aqueous oxygen-saturated solutions of Hematoporphyrin and Rose Bengal in 90% D2O using a sensitive new reagent which reacts specifically with singlet oxygen to produce an EPR detectable signal .Our results were inconsistent with a major role for singlet oxygen formation in the sonolysis of these compounds. The role of the hydrophobicity of sonosensitzers in determining their accumulation at the water - gas interface of ultrasound-induced cavitation bubbles is being studied by considering the Gibbs surface excess and the possible role of the dynamic surface tension using model surfactant molecules.Recent Publications:Misik,V., Miyoshi,N. and Riesz,P. Free Rad Biol Med 26:961-67, 1999.Misik,V. and Riesz,P. in "Sonochemistry and Sonoluminescence"ed.L.A.Crum et al. (eds.) NATO ASI Series,Kluwer Academic Publishers, 225-236, 1999Misik, V. and Riesz, P. Ann. New York Acad. Sci., 899:335-348, 2000.Miyoshi, N., Igarashi, T. and Riesz, P. Ultrasonics-Sonochemistry, 7:121-124, 2000.