RADIOLYSIS, PHOTOLYSIS AND SONOLYSIS OF CELLS AND THEIR CONSTITUENTS

工作概述：声动力疗法是一种很有前景的癌症治疗新方式，它基于药物（声敏剂，通常是卟啉）和超声联合杀伤细胞的协同作用。声动力疗法的有效性已在细胞研究和荷瘤动物中得到证实。这种药物依赖性声致敏的机制尚不清楚，但不同种类的声致敏剂可能有不同的声致敏机制。作为阐明这些机制的一部分，我们使用电子顺磁共振（EPR）和自旋捕获技术研究了超声波暴露典型细胞培养基（RPM-1640）时产生的自由基和过氧化氢。细胞暴露在超声波下产生的自由基和/或过氧化氢具有潜在的细胞毒性和致突变性。自由基的形成和类型可以通过对细胞进行超声照射的介质的化学成分进行实质性的调节。在本研究中，我们检测了典型细胞培养基（RPMI-1640）超声暴露过程中形成的自由基中间体；通过自旋捕获鉴定的主要自由基来自疏水氨基酸Trp、Leu和Phe，并通过从这些氨基酸中提取氢而形成。与磷酸盐缓冲盐水相比，细胞培养液中OH自由基和h2o2的产量显著降低，葡萄糖（培养基的主要有机成分）和疏水氨基酸（Trp, Phe, Tyr, Val, Met）是造成这种影响的主要原因。相比之下，其他非疏水氨基酸对蛋白质活性的贡献不显著。OH或H2O2减少。这些发现与疏水溶质在塌陷空化气泡的液气界面积聚导致自由基清除效率提高相一致。最近的出版物:近藤T Misik, V。和黎兹,P。中国生物医学工程学报（英文版）；2008;25(5):591 - 591。和黎兹,P。1999；26:936 - 43 misik, V。三好,N。和黎兹,P。1999；26:961 - 67 misik, V。和黎兹,P。在声化学与声致发光 d.l a。Crum等人编。北约ASI系列，Kluwer学术出版社，225-236,1999 -癌症，电子顺磁共振（EPR），声化学，声动力治疗，自旋俘获，超声，

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,