Misik V, Riesz P
Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Free Radic Biol Med. 1996;20(1):129-38. doi: 10.1016/0891-5849(95)02009-8.
Sonodynamic therapy, which refers to a synergistic effect of drugs and ultrasound, is a promising new modality for cancer treatment. The sonodynamic effect was found for a number of structurally unrelated compounds, and the underlying mechanisms are still unknown. Recently, Jeffers et al. (J. Acoust. Soc. Am. 97:669-676; 1995) have shown that the sonodynamic action of nontoxic concentrations of N,N-dimethylformamide (DMF), N-methyl formamide (MMF), and dimethylsulfoxide (DMSO) combined with ultrasound, on killing of cultured HL-60 human promyelocytic leukemia cells, and attributed this toxic effect to unknown short lived reactive species produced from these solutes by ultrasonic cavitation. Using the spin trap 3,5-dibromo-4-nitrosobenzene sulfonate (DBNBS) in nitrogen-saturated aqueous solutions of DMF, MMF, or DMSO exposed to 50 kHz ultrasound, we detected formation of .CH3 and .CH2N(CH3)CHO radical adducts for DMF, mostly .CH2NHCHO adducts for MMF, and .CH3 adducts for DMSO. These radicals were formed either by reactions of the solutes with ultrasound-generated .H and .OH radicals (such as .CH2R-type radicals in DMF and MMF, and .CH3 radicals in DMSO), or by direct pyrolysis of the weak bonds in the solute molecules (e.g., .CH3 radicals from DMF). In air-saturated sonicated solutions these carbon centered radicals were converted to the corresponding peroxyl radicals and spin trapped with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO); .OOCH2N(CH3)CHO radicals were identified in DMF, .OOCH2NHCHO radicals in MMF, and .OOCH3 radicals in DMSO solutions. We suggest that these radical species by virtue of their longer lifetimes and higher selectivity, compared to .OH radicals, which are also formed in sonicated solutions, are the species responsible for sonodynamic cell killing by the combined effect of ultrasound with DMF, MMF, or DMSO.
声动力疗法是指药物与超声的协同作用，是一种很有前景的癌症治疗新方法。已发现多种结构不相关的化合物具有声动力效应，但其潜在机制仍不清楚。最近，杰弗斯等人（《美国声学学会杂志》97:669 - 676；1995年）表明，无毒浓度的N，N - 二甲基甲酰胺（DMF）、N - 甲基甲酰胺（MMF）和二甲基亚砜（DMSO）与超声联合作用对培养的HL - 60人早幼粒细胞白血病细胞具有声动力作用，并将这种毒性作用归因于这些溶质通过超声空化产生的未知短寿命活性物质。在暴露于50 kHz超声的DMF、MMF或DMSO的氮气饱和水溶液中使用自旋捕获剂3,5 - 二溴 - 4 - 亚硝基苯磺酸盐（DBNBS），我们检测到DMF形成了·CH₃和·CH₂N(CH₃)CHO自由基加合物，MMF主要形成·CH₂NHCHO加合物，DMSO形成·CH₃加合物。这些自由基要么是溶质与超声产生的·H和·OH自由基反应形成的（如DMF和MMF中的·CH₂R型自由基以及DMSO中的·CH₃自由基），要么是溶质分子中弱键的直接热解形成的（例如DMF中的·CH₃自由基）。在空气饱和的超声处理溶液中，这些以碳为中心的自由基转化为相应的过氧自由基并用5,5 - 二甲基 - 1 - 吡咯啉 - N - 氧化物（DMPO）进行自旋捕获；在DMF中鉴定出·OOCH₂N(CH₃)CHO自由基，在MMF中鉴定出·OOCH₂NHCHO自由基，在DMSO溶液中鉴定出·OOCH₃自由基。我们认为，与超声处理溶液中也会形成的·OH自由基相比，这些自由基物种凭借其更长的寿命和更高的选择性，是超声与DMF、MMF或DMSO联合作用导致声动力细胞杀伤作用的原因。
