Pan Yan, Yuan Dexiao, Zhang Junxiang, Xu Ping, Chen Honghong, Shao Chunlin
Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.
Radiat Res. 2009 Apr;171(4):446-53. doi: 10.1667/RR1491.1.
The combined exposure to environmental toxicants such as heavy metals and radiation is an important research area in health protection. The aim of this study was to investigate the role of DNA repair and the phosphatidylinositol 3-kinase (PI3K) family in the cadmium-induced adaptive response to toxicants or radiation. Using cells of three Chinese hamster ovary (CHO) cell lines with different capacities to repair DNA damage, we found that pre-exposure to cadmium at a nonlethal concentration could induce an adaptive response to a subsequent challenge with cadmium or radiation in all the cell lines. The magnitude of the adaptive response in adapted cells was dependent on several factors, including DNA repair capacity, the priming dose of cadmium, and the challenging dose of cadmium or radiation. When the cells were challenged with 50 microM CdCl2, the adaptive response was less evident in XRCC1-defective EM-C11 cells than in cells of the other two cell lines. Moreover, treatment of cells with wortmannin or KU-55933 eliminated the adaptive response in all the cell lines. Our data suggest that the triggering of a cadmium-induced adaptive response was independent of DNA repair capacity. Single-strand break (SSB) repair or base excision repair (BER) rather than double-strand break (DSB) repair was mainly involved in the adaptive response. This response of cells to a further challenge with cadmium or radiation may be mediated through the ataxia telangiectasia mutated (ATM) pathway.
接触重金属和辐射等环境毒物的综合影响是健康保护领域的一个重要研究方向。本研究旨在探讨DNA修复及磷脂酰肌醇3激酶（PI3K）家族在镉诱导的对毒物或辐射的适应性反应中的作用。我们使用了三种具有不同DNA损伤修复能力的中国仓鼠卵巢（CHO）细胞系，发现以非致死浓度预先接触镉能够在所有细胞系中诱导对随后镉或辐射刺激的适应性反应。适应性细胞中适应性反应的强度取决于多个因素，包括DNA修复能力、镉的预刺激剂量以及镉或辐射的刺激剂量。当细胞受到50微摩尔氯化镉刺激时，XRCC1缺陷的EM-C11细胞中的适应性反应不如其他两种细胞系明显。此外，用渥曼青霉素或KU-55933处理细胞消除了所有细胞系中的适应性反应。我们的数据表明，镉诱导的适应性反应的触发与DNA修复能力无关。单链断裂（SSB）修复或碱基切除修复（BER）而非双链断裂（DSB）修复主要参与了适应性反应。细胞对镉或辐射进一步刺激的这种反应可能通过共济失调毛细血管扩张症突变（ATM）途径介导。
