D-methionine (D-met), a dextrorotatory isoform of the amino acid L-methionine (L-met), can prevent oral mucositis and salivary hypofunction in mice exposed to radiation. However, the mechanism of its radioprotection is unclear, especially with regard to the stereospecific functions of D-met. Radiation is known to cause injury to normal tissue by triggering DNA damage in cells. Thus, in this study we sought to determine whether the chirality of D-/L-met affects radiation-induced events at the DNA level. We selected plasmid DNA assays to examine this effect in vitro, since these assays are highly sensitive and allow easy detection of DNA damage. Samples of supercoiled pBR322 plasmid DNA mixed with D-met, L-met or dimethylsulfoxide (DMSO) were prepared and irradiated with a Bragg peak beam of carbon ions (∼290 MeV/u) with a 6-cm spread. DNA strand breaks were indicated by the change in the form of the plasmid and were subsequently quantified using agarose gel electrophoresis. We found that D-met yielded approximately equivalent protection from carbon-ion-induced DNA damage as DMSO. Thus, we propose that the protective functions of methionine against plasmid DNA damage could be explained by the same mechanism as that for DMSO, namely, hydroxyl radical scavenging. This stereospecific radioprotective mechanism occurred at a level other than the DNA level. There was no significant difference between the radioprotective effect of D-met and L-met on DNA.

中文翻译：

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D-蛋氨酸对治疗性碳离子诱导的质粒DNA损伤的保护作用的潜在机制。

D-蛋氨酸（D-met）是氨基酸L-蛋氨酸（L-met）的右旋同种型，可以预防暴露于辐射的小鼠的口腔粘膜炎和唾液功能减退。但是，其放射防护的机制尚不清楚，尤其是在D-met的立体定向功能方面。已知辐射会通过触发细胞中的DNA损伤而对正常组织造成伤害。因此，在这项研究中，我们试图确定D- / L-met的手性是否在DNA水平上影响辐射诱导的事件。我们选择了质粒DNA分析法来体外测试这种效果，因为这些分析法非常灵敏，可以轻松检测DNA损伤。制备与D-met，L-met或二甲基亚砜（DMSO）混合的超螺旋pBR322质粒DNA样品，并用6厘米宽的碳离子的布拉格峰束（〜290 MeV / u）照射。DNA链断裂由质粒形式的变化指示，随后使用琼脂糖凝胶电泳进行定量。我们发现，D-met与DMSO相比，对碳离子诱导的DNA损伤产生了大致相同的保护。因此，我们提出蛋氨酸对质粒DNA损伤的保护功能可以用与DMSO相同的机理来解释，即清除羟基自由基。该立体特异性放射防护机制发生在DNA水平以外的水平。D-met和L-met对DNA的放射防护作用之间没有显着差异。因此，我们提出蛋氨酸对质粒DNA损伤的保护功能可以用与DMSO相同的机理来解释，即清除羟基自由基。该立体特异性放射防护机制发生在DNA水平以外的水平。D-met和L-met对DNA的放射防护作用之间没有显着差异。因此，我们提出蛋氨酸对质粒DNA损伤的保护功能可以用与DMSO相同的机理来解释，即清除羟基自由基。该立体特异性放射防护机制发生在DNA水平以外的水平。D-met和L-met对DNA的放射防护作用之间没有显着差异。