Abt G, Vaghef H, Gebhart E, Dahlgren C V, Hellman B
Institute of Human Genetics, University of Erlangen-Nürnberg, Germany.
Mutat Res. 1997 Jun 9;384(1):55-64. doi: 10.1016/s0921-8777(97)00013-x.
Samples of human whole blood from 8 different donors were incubated with physiological saline or N-acetyl-L-cysteine (NAC, 1 x 10(-3) M) before being irradiated in vitro with high-energy X-rays (0.7 or 2.0 Gy). Primary DNA damage was evaluated in isolated lymphocytes using alkaline single-cell gel electrophoresis. Whereas the lymphocytes from non-irradiated blood samples showed a similar 'background level' of damage, there was a difference in sensitivity towards the radiation-induced DNA damage, especially at 2.0 Gy. When the data were pooled there was a clear and dose-related increase (p < 0.001) in damage, both in the absence and presence of NAC. Using the two most sensitive 'comet parameters' for DNA damage, i.e., the tail inertia and tail moment, the radiation-induced damage was found to be significantly increased already at 0.7 Gy in the samples that had been irradiated without NAC. Overall, NAC was found to be without radioprotective effects. Instead, the incubation with NAC itself was found to be associated with a slightly increased level of DNA damage. If the present findings are relevant also in an in vivo situation using peripheral lymphocytes as a surrogate for non-malignant cells in the body, NAC seems to be of limited value as a radioprotective agent in the clinic, at least when it comes to the acute DNA-damaging effects of therapeutic doses of high-energy X-rays.
来自8位不同捐赠者的人体全血样本，在体外接受高能X射线（0.7或2.0 Gy）照射之前，先用生理盐水或N - 乙酰 - L - 半胱氨酸（NAC，1×10⁻³ M）进行孵育。使用碱性单细胞凝胶电泳法对分离出的淋巴细胞中的原发性DNA损伤进行评估。未照射的血液样本中的淋巴细胞显示出相似的“背景损伤水平”，但对辐射诱导的DNA损伤的敏感性存在差异，尤其是在2.0 Gy时。当汇总数据时，无论有无NAC，损伤均有明显的剂量相关增加（p < 0.001）。使用两个对DNA损伤最敏感的“彗星参数”，即尾部惯性和尾部矩，发现在未用NAC照射的样本中，在0.7 Gy时辐射诱导的损伤就已显著增加。总体而言，发现NAC没有辐射防护作用。相反，发现用NAC孵育本身与DNA损伤水平略有增加有关。如果目前的研究结果在体内情况下也相关，以外周血淋巴细胞作为体内非恶性细胞的替代物，那么NAC作为临床辐射防护剂的价值似乎有限，至少在涉及治疗剂量高能X射线的急性DNA损伤效应方面是这样。
