RADIOLYSIS, PHOTOLYSIS AND SONOLYSIS OF CELLS AND THEIR CONSTITUENTS

细胞及其成分的放射分解、光分解和声分解

• 批准号: 3752332
• 负责人: P RIESZ
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3752332
• 关键词: combination cancer therapy; cytolysis; dimethylsulfoxide; drug interactions; electron spin resonance spectroscopy; free radical scavengers; neoplasm /cancer photoradiation therapy; neoplasm /cancer radiation therapy; neoplasm /cancer therapy; photolysis; photosensitizing agents; radiosensitizer; superoxide dismutase; ultrasound biological effect; ultrasound therapy

Recently there has been renewed interest in the use of ultrasound for cancer therapy since the combination of ultrasound and hematoporphyrin, a photochemical sensitizer for tumor treatment in photodynamic therapy, showed marked synergistic effects on the inhibition of tumor growth. Sonosensitization, a term that can be used to describe the potentiation of drug toxicity by ultrasound, was also found for adriamycin, daunomycin, diaziquone, and also for organic solvents dimethylsulfoxide, and N, N- dimethylformamide (DMF). Currently, the underlying mechanisms of the synergistic effects of drugs and ultrasound on cell killing are not understood and need further investigations. The understanding of the mechanism of drug/ultrasound synergism is essential for possible further therapeutic applications of sonosensitizing therapy in tumor treatment. Electron spin resonance and spin trapping methods were used to investigate the sonochemistry of DMF/water mixtures using the spin trap 3,5-dibromo-4- nitrosobenzene sulfonate (DBNBS). The methyl and H2CN(CH3)C(O)H radicals were spin trapped with DBNBS in aqueous DMF mixtures exposed to 5OkHz ultrasound under argon. The yields of these radical adducts increase with increasing molar fraction of DMF. This behavior is different from the previously investigated aqueous mixtures of organic solvents with vapor pressures higher than water, which results in dampening of the cavitation events due to the effect of =Cp/Cv. In addition to the radicals spin trapped in queous DMF mixtures the N(CH3)R radical were detected using the spin trap nitrosodurene (ND) in sonolysis of pure DMF. The kinetic isotope effect, kH/kD, for the ultrasound-induced production of 'CHRR' and 'CDRR' radicals in mixtures of n-dodecane/n-dodecane-d26 and toluene/toluene-d8 was used to probe the temperatures of various sonochemical reaction regions: the temperature of the region of hydrogen abstraction radical formation ('CHRR') in n-dodecane was estimated to be 75O+/- 150 K; the effective temperature of the region where benzyl radicals are formed from toluene by sonochemical pyrolysis was estimated to be about 6000K. This method appears to be a promising tool for probing the temperatures of different sonochemical regions and mechanisms of the processes involved in sonodynamic interactions.

最近，人们重新对超声用于 自超声波和血卟啉联合治疗癌症以来， 光动力疗法中用于肿瘤治疗的光化学敏化剂， 对肿瘤生长的抑制有明显的协同作用。 声致敏，一个术语，可用于描述增强的 药物毒性，也发现阿霉素，道诺霉素， 重氮醌，也用于有机溶剂二甲亚砜，和N，N- 二甲基甲酰胺（DMF）。 目前， 药物和超声波对细胞杀伤的协同作用并不 了解并需要进一步调查。 的理解 药物/超声协同作用的机制对于可能的进一步的 声敏疗法在肿瘤治疗中的治疗应用。 用电子自旋共振和自旋捕获方法研究了 使用自旋阱3，5-二溴-4-（三氟甲基）-N-甲基-N-甲酰胺（DMF）/水混合物的声化学 亚硝基苯磺酸盐（DBNBS）。 甲基和H2 CN（CH 3）C（O）H基团 的自旋捕获与DBNBS在DMF水溶液的混合物暴露于50 kHz 在氩气下超声。这些自由基加合物的产率随着 增加DMF的摩尔分数。此行为不同于 先前研究的有机溶剂与蒸气的含水混合物 压力高于水，这导致气穴的衰减 由于=Cp/Cv的影响而发生的事件。 除了自由基自旋 在DMF混合水溶液中捕获的N（CH 3）R自由基， 在纯DMF超声分解中自旋捕获亚硝基杜烯（ND）。 动力学 同位素效应，kH/kD，用于超声诱导的“CHRR”产生， 正十二烷/正十二烷-d26和 甲苯/甲苯-D8用于探测各种温度， 声化学反应区域：氢气区域的温度 正十二烷中的提取自由基形成（“CHRR”）估计为 75 O +/- 150 K;苄基 估计了甲苯通过声化学热解形成的自由基 大约是6000 K。 这种方法似乎是一种很有前途的工具， 不同声化学区域的温度和声化学的机理 涉及声动力相互作用的过程。