Hartwig A, Beyersmann D
Department of Biology and Chemistry, University of Bremen, F.R.G.
Mutat Res. 1989 Jan;217(1):65-73. doi: 10.1016/0921-8777(89)90037-2.
With regard to contradictory results concerning the mutagenicity of nickel compounds in short-term assays, especially in bacterial test systems, Chinese hamster V79 cells were used to measure mutagenicity, comutagenicity and the induction of sister-chromatid exchanges (SCEs) by NiCl2. We confirmed the induction of mutations at the HGPRT locus as well as SCEs. In addition, NiCl2 shows a pronounced comutagenic effect towards UV. When using confluent cultures or resting cells due to serum deprivation, where more time is given for repair processes, the comutagenic effect is higher compared to logarithmically growing cells (10 and 4 times, respectively, compared to twice). Hence, we attribute this enhancement in mutagenicity to inhibition of DNA repair. Also the increase in induced SCEs after combined treatment with UV and NiCl2 supports this thesis. Furthermore, NiCl2 enhances the cyto-toxicity of cis-DDP about 12-fold. Since no comutagenic effect is observed in combination with MMS, we suggest that the inhibition of DNA repair by Ni(II) applies to all DNA changes that are repaired by the 'long-patch' excision repair system. This inhibition may occur via replacement of other divalent metal ions essential in repair and regulation processes.
关于镍化合物在短期试验，尤其是细菌试验系统中致突变性的矛盾结果，我们使用中国仓鼠V79细胞来检测氯化镍的致突变性、共诱变作用以及对姐妹染色单体交换（SCEs）的诱导作用。我们证实了在次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶（HGPRT）位点的突变诱导以及SCEs的诱导。此外，氯化镍对紫外线显示出明显的共诱变作用。当使用汇合培养物或由于血清剥夺而处于静止状态的细胞时，由于有更多时间进行修复过程，与对数生长期细胞相比，共诱变作用更高（分别是10倍和4倍，而不是两倍）。因此，我们将这种致突变性的增强归因于DNA修复的抑制。紫外线和氯化镍联合处理后诱导的SCEs增加也支持这一论点。此外，氯化镍将顺铂的细胞毒性提高了约12倍。由于未观察到与甲基磺酸甲酯（MMS）联合的共诱变作用，我们认为镍（II）对DNA修复的抑制适用于所有由“长补丁”切除修复系统修复的DNA变化。这种抑制可能是通过取代修复和调节过程中必需的其他二价金属离子而发生的。
