Lee-Chen S F, Wang M C, Yu C T, Wu D R, Jan K Y
Institute of Zoology, Academia Sinica, Taipei, Republic of China.
Biol Trace Elem Res. 1993 Apr;37(1):39-50. doi: 10.1007/BF02789400.
Nickel, a human carcinogen, has been shown to enhance the cytotoxicity, mutagenicity, and sister-chromatid exchanges (SCE) induced by ultraviolet (UV) light but not by methyl methanesulfonate (MMS). To verify that the cocytotoxicity and cogenotoxicity of nickel are correlated with its inhibition on DNA repair, the effects of nickel on the DNA repair induced by UV and by MMS have been investigated. Our analyses of DNA repair of single-strand breaks by alkaline elution and alkaline sucrose sedimentation indicate that nickel inhibited the DNA repair in UV-treated, but not in MMS-treated cells. Therefore, the inhibition of DNA repair seems to play an important role in the cocytotoxicity and comutagenicity of nickel. However, the inhibition of DNA repair seems not to play a decisive role in enhancing SCE, because we have previously shown that arsenite inhibits the UV-induced DNA repair, but has no enhancing effect on the UV-induced SCE. Our results also show that nickel had obvious inhibitory effects on DNA ligation and postreplication repair, but had no apparent effect on nucleotide excision and DNA polymerization in the UV repair. The results of the DNA ligation inhibition by nickel in UV but not in MMS repair suggest that different ligases are used in the DNA repair of UV- and MMS-induced damages.
镍是一种人类致癌物，已被证明可增强紫外线（UV）诱导的细胞毒性、致突变性和姐妹染色单体交换（SCE），但对甲磺酸甲酯（MMS）诱导的这些效应无增强作用。为了验证镍的共细胞毒性和共遗传毒性是否与其对DNA修复的抑制作用相关，研究了镍对紫外线和甲磺酸甲酯诱导的DNA修复的影响。我们通过碱性洗脱和碱性蔗糖沉降对单链断裂的DNA修复进行分析，结果表明镍抑制紫外线处理细胞中的DNA修复，但不抑制甲磺酸甲酯处理细胞中的DNA修复。因此，DNA修复的抑制似乎在镍的共细胞毒性和共致突变性中起重要作用。然而，DNA修复的抑制在增强SCE方面似乎不起决定性作用，因为我们之前已经表明亚砷酸盐抑制紫外线诱导的DNA修复，但对紫外线诱导的SCE没有增强作用。我们的结果还表明，镍对DNA连接和复制后修复有明显的抑制作用，但对紫外线修复中的核苷酸切除和DNA聚合没有明显影响。镍在紫外线而非甲磺酸甲酯修复中抑制DNA连接的结果表明，紫外线和甲磺酸甲酯诱导损伤的DNA修复使用了不同的连接酶。
