Induction and repair of formaldehyde-induced DNA-protein crosslinks in repair-deficient human cell lines
Induction and repair of formaldehyde-induced DNA-protein crosslinks in repair-deficient human cell lines
复制标题
DOI：
10.1093/mutage/15.1.85
复制
发表时间：
2000-01-01
期刊：
影响因子：
2.7
通讯作者：
Merk, O
中科院分区：
文献类型：
--
作者：
Speit, G;Schütz, P;Merk, O
我们以前已经表明，碱性彗星试验（单细胞凝胶电泳）在一个修改的版本是一个敏感的检测甲醛诱导的DNA-蛋白质交联（DPC）的测试。我们的研究结果还表明，甲醛诱导的DPC与染色体效应如微核和姐妹染色单体交换的形成有关。为了更好地理解甲酰胺诱导的DPC的遗传后果，我们现在研究了DPC的诱导和去除与正常和修复缺陷人类细胞系中微核形成的关系。我们没有发现正常细胞、着色性干皮病（XP）细胞系和范可尼贫血（FA）细胞系之间在DPC的诱导和去除方面存在显著差异。然而，在相同的处理条件下，在两种修复缺陷细胞系中，特别是在XP细胞中，微核的诱导增强。与DNA-DNA交联剂丝裂霉素C（MMC）的比较研究显示，在两种修复缺陷细胞系中，交联的延迟去除和微核的诱导增强。发现FA细胞对MMC的微核诱导特别敏感。与甲醛的结果相反，MMC诱导微核的浓度远低于彗星试验中的影响。我们的研究结果表明，一个以上的修复途径可以参与修复的交联和干扰切除修复甲醛处理后的染色体畸变的形成方面有更严重的后果比干扰交联修复。
We have previously shown that the alkaline Comet assay (single cell gel electrophoresis) in a modified version is a sensitive test for the detection of formaldehyde-induced DNA-protein crosslinks (DPC). Our results also indicated that formaldehyde-induced DPC are related to the formation of chromosomal effects such as micronuclei and sister chromatid exchanges. To better understand the genetic consequences of formaldehyde-induced DPC we have now investigated the induction and removal of DPC in relationship to the formation of micronuclei in normal and repair-deficient human cell lines, We did not find significant differences between normal cells, a xeroderma pigmentosum (XP) cell line and a Fanconi anaemia (FA) cell line with respect to the induction and removal of DPC, However, the induction of micronuclei was enhanced in both repair-deficient cell lines, particularly in XP cells, under the same treatment conditions. Comparative investigations with the DNA-DNA crosslinker mitomycin C (MMC) revealed a delayed removal of crosslinks and enhanced induction of micronuclei in both repair-deficient cell lines. FA cells were found to be particularly hypersensitive to micronucleus induction by MMC, In contrast to the results with formaldehyde, induction of micronuclei by MMC occurred at much lower concentrations than the effects in the Comet assay. Our results suggest that more than one repair pathway can be involved in the repair of crosslinks and that disturbed excision repair has more severe consequences with regard to the formation of chromosomal aberrations after formaldehyde treatment than has disturbed crosslink repair.