Reactive oxygen species are involved in nickel inhibition of DNA repair
Reactive oxygen species are involved in nickel inhibition of DNA repair
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DOI：
10.1002/(sici)1098-2280(1997)29:2
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发表时间：
1997
影响因子：
2.8
通讯作者：
S. Lynn;F. Yew;K. Chen;K. Jan
中科院分区：
文献类型：
--
作者：
S. Lynn;F. Yew;K. Chen;K. Jan
镍已被证明可以抑制DNA修复的方式，可能在其毒性中发挥作用。由于镍治疗增加细胞活性氧（ROS），我们已经调查了参与镍抑制DNA修复的ROS。谷胱甘肽合成或过氧化氢酶活性的抑制增加了镍对紫外线（UV）光的细胞毒性的增强作用。抑制过氧化氢酶和谷胱甘肽过氧化物酶活性也增强了镍对紫外线照射细胞中由羟基脲和胞嘧啶-β-D-阿拉伯呋喃糖苷积累的DNA链断裂重新连接的阻滞作用。由于DNA聚合和连接参与了DNA断裂的重新连接，我们在中国仓鼠卵巢细胞提取物中研究了ROS对这两个步骤的影响。镍对（3 H）dTTP掺入DNase I激活的小牛胸腺DNA的抑制作用强于poly（dA）oligo（dT）的连接，而H2 O2对DNA连接的抑制作用强于DNA聚合。镍，在H2 O2的存在下，表现出协同抑制DNA聚合和连接，并导致蛋白质片段化。此外，谷胱甘肽可以完全恢复镍或H2 O2单独的抑制，但只有部分恢复镍和H2 O2的抑制。因此，镍可能与DNA修复酶结合并产生氧自由基，导致蛋白质原位降解。这种对参与DNA修复、复制、重组和转录的蛋白质的不可逆损伤可能对镍的毒性作用很重要。Environ.摩尔变异体29：208-216，1997.© 1997 Wiley利斯公司
Nickel has been shown to inhibit DNA repair in a way that may play a role in its toxicity. Since nickel treatment increases cellular reactive oxygen species (ROS), we have investigated the involvement of ROS in nickel inhibition of DNA repair. Inhibition of glutathione synthesis or catalase activity increased the enhancing effect of nickel on the cytotoxicity of ultraviolet (UV) light. Inhibition of catalase and glutathione peroxidase activities also enhanced the retardation effect of nickel on the rejoining of DNA strand breaks accumulated by hydroxyurea plus cytosine‐β‐D‐arabinofuranoside in UV‐irradiated cells. Since DNA polymerization and ligation are involved in the DNA‐break rejoining, we have investigated the effect of ROS on these two steps in an extract of Chinese hamster ovary cells. Nickel inhibition of the incorporation of (3H)dTTPinto the DNase I‐activated calf thymus DNA was stronger than the ligation of poly(dA)oligo(dT), whereas H2O2 was more potent in inhibiting DNA ligation than DNA polymerization. Nickel, in the presence of H2O2, exhibited a synergistic inhibition on both DNA polymerization and ligation and caused protein fragmentation. In addition, glutathione could completely recover the inhibition by nickel or H2O2 alone but only partially recover the inhibition by nickel plus H2O2. Therefore, nickel may bind to DNA‐repair enzymes and generate oxygen‐free radicals to cause protein degradation in situ. This irreversible damage to the proteins involved in DNA repair, replication, recombination, and transcription could be important for the toxic effects of nickel. Environ. Mol. Mutagen. 29:208–216, 1997. © 1997 Wiley‐Liss, Inc.