Woźniak Katarzyna, Błasiak Janusz
Department of Molecular Genetics, University of Łódź, Banacha 12/16, 90-237 Łódź, Poland.
Cell Mol Biol Lett. 2004;9(1):83-94.
Nickel(II) is reported to be genotoxic, but the mechanisms underlying its genotoxicity are largely unknown. It can interfere with DNA repair and this may contribute to its genotoxicity. We studied the effect of nickel chloride on the repair of DNA damaged by UV radiation or N-methyl-N-nitro-N-nitrosoguanidine (MNNG) in human lymphocytes using the alkaline comet assay. Nickel(II) at 1 microM caused an accumulation of DNA breaks during repair incubation, which could follow from the inhibition of the polymerization/ligation step of UV-damaged DNA repair. On the other hand, nickel(II) inhibited the formation of transient DNA breaks brought by the repair process after incubation with MNNG at 5 microM, which might follow from interference with the recognition/incision step of excision repair. Additionally, nickel at 1 microM inhibited the activity of formamidopyrimidine-DNA glycosylase (Fpg) and 3-methyladenine-DNA glycosylase II (Alk A), enzymes involved in DNA excision repair. A decrease in endonuclease III (Endo III) activity was observed at 2 and 5 microM of nickel chloride. Our results suggest that nickel(II) at non-cytotoxic concentrations can inhibit various steps of DNA excision repair, and this may contribute to its genotoxicity.
据报道，镍（II）具有基因毒性，但其基因毒性的潜在机制在很大程度上尚不清楚。它会干扰DNA修复，这可能是其基因毒性的原因之一。我们使用碱性彗星试验研究了氯化镍对人淋巴细胞中紫外线辐射或N-甲基-N-硝基-N-亚硝基胍（MNNG）损伤的DNA修复的影响。1微摩尔的镍（II）在修复孵育过程中导致DNA断裂的积累，这可能是由于紫外线损伤的DNA修复的聚合/连接步骤受到抑制所致。另一方面，镍（II）抑制了在5微摩尔MNNG孵育后修复过程带来的瞬时DNA断裂的形成，这可能是由于干扰了切除修复的识别/切割步骤所致。此外，1微摩尔的镍抑制了参与DNA切除修复的甲酰胺嘧啶-DNA糖基化酶（Fpg）和3-甲基腺嘌呤-DNA糖基化酶II（Alk A）的活性。在2和5微摩尔的氯化镍浓度下观察到核酸内切酶III（Endo III）活性降低。我们的结果表明，非细胞毒性浓度的镍（II）可以抑制DNA切除修复的各个步骤，这可能是其基因毒性的原因之一。
