Cobalt(II) inhibits the incision and the polymerization step of nucleotide excision repair in human fibroblasts
Cobalt(II) inhibits the incision and the polymerization step of nucleotide excision repair in human fibroblasts
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DOI：
10.1016/s0921-8777(96)00052-3
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发表时间：
1997-01-31
期刊：
影响因子：
--
通讯作者：
Hartwig, A
中科院分区：
文献类型：
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作者：
Kasten, U;Mullenders, LHF;Hartwig, A
钴化合物对实验动物有致癌作用，但对体外培养的哺乳动物细胞的致突变性较弱。相反，钴(II)已被证明抑制紫外线诱导的DNA损伤的去除，这表明干扰了细胞DNA修复过程。在本研究中，研究了钴(II)影响核苷酸切除修复的哪一步及其涉及的机制。在此背景下，用碱性解离技术在不同条件下检测了非细胞毒性钴(II)浓度对UVC诱导的人成纤维细胞DNA损伤的诱导和修复的影响。钴(II)浓度低至50微米，对切割和聚合步骤均有抑制作用。相反，修复补片的连接不受该金属的干扰，结合碱性解卷技术和修复酶T4核酸内切酶V，证明了环丁烷嘧啶二聚体在150 mM或更高的浓度下，其切割会受到影响。作为一种作用模式，钴(II)离子与必需的镁(II)离子的竞争是可以确定的。
Compounds of cobalt are carcinogenic to experimental animals, but the mutagenicity in mammalian cells in culture is rather weak. In contrast, cobalt(II) has been shown to inhibit the removal of DNA damage induced by UVC light, indicating an interference with cellular DNA repair processes. In the present study it was investigated which step of the nucleotide excision repair is affected by cobalt(II) and which mechanisms are involved. In this context, the effect of non-cytotoxic cobalt(II) concentrations on the induction as well as on the repair of UVC-induced DNA lesions has been examined in human fibroblasts by using the alkaline unwinding technique under various conditions. Cobalt(II) concentrations as low as 50 mu M inhibit the incision as well as the polymerization step. In contrast, the ligation of repair patches is not disturbed by this metal, By combining the alkaline unwinding technique with the repair enzyme T4 endonuclease V, it is demonstrated that the incision at the site of cyclobutane pyrimidine dimers is affected at concentrations of 150 mu M and higher. As one mode of action, the competition with essential magnesium(II) ions by cobalt(II) ions could be identified.