Cramers Patricia, Atanasova Petya, Vrolijk Hans, Darroudi Firouz, van Zeeland Albert A, Huiskamp René, Mullenders Leon H F, Kleinjans Jos C S
Department of Toxicogenetics, Leiden University Medical Center, Leiden, The Netherlands.
Radiat Res. 2005 Oct;164(4 Pt 1):383-90. doi: 10.1667/rr3430.1.
The adaptive response to ionizing radiation may be mediated by the induction of antioxidant defense mechanisms, accelerated repair or altered cell cycle progression after the conditioning dose. To gain new insight into the mechanism of the adaptive response, nondividing lymphocytes and fibroblasts were used to eliminate possible contributions of cell cycle effects. The effect of conditioning doses of 0.05 or 0.1 Gy followed by challenging doses up to 8 Gy (with a 4-h interval between exposures) on induction and repair of DNA damage was determined by single-cell gel electrophoresis (comet assay), premature chromosome condensation, and immunofluorescence labeling for gamma-H2AX. The conditioning dose reduced the induction of DNA strand breaks, but the kinetics of strand break rejoining was not influenced by the conditioning dose in nondividing cells of either cell type. We conclude that adaptation in nondividing cells is not mediated by enhanced strand break rejoining and that protection against the induction of DNA damage is rather small. Therefore, the adaptive response is most likely a reflection of perturbation of cell cycle progression.
对电离辐射的适应性反应可能是由抗氧化防御机制的诱导、预处理剂量后加速修复或改变细胞周期进程介导的。为了深入了解适应性反应的机制,使用非分裂淋巴细胞和成纤维细胞来排除细胞周期效应的可能影响。通过单细胞凝胶电泳(彗星试验)、早熟染色体凝集以及γ-H2AX免疫荧光标记,确定了0.05或0.1 Gy的预处理剂量,随后给予高达8 Gy的激发剂量(两次照射间隔4小时)对DNA损伤诱导和修复的影响。预处理剂量减少了DNA链断裂的诱导,但在两种细胞类型的非分裂细胞中,链断裂重新连接的动力学不受预处理剂量的影响。我们得出结论,非分裂细胞中的适应性不是由增强的链断裂重新连接介导的,并且对DNA损伤诱导的保护作用相当小。因此,适应性反应很可能是细胞周期进程受到扰动的一种反映。