Relationship between DNA lesions, DNA repair and chromosomal damage induced by acetaldehyde

Relationship between DNA lesions, DNA repair and chromosomal damage induced by acetaldehyde
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DOI:
10.1016/j.mrfmmm.2008.11.008
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发表时间:
2009-03-09
影响因子:
2.3
通讯作者:
Palitti, Fabrizio
Palitti, Fabrizio
中科院分区:
医学4区
文献类型:
--
作者:
Garcia, Claudia Lorenti;Mechilli, Manuela;Palitti, Fabrizio

文献摘要

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沿着两种其它交联剂测试乙醛(AA):甲醛(FA),DNA-蛋白质交联(DPC)的诱导剂和丝裂霉素C(MMC),链间交联(ICL)的诱导剂,以找出AA的作用机制是否更类似于MMC或FA。使用彗星试验的标准方案的修改,我们证明AA诱导交联,使用碱性彗星形式和蛋白酶-K的组合,观察到AA诱导的DNA迁移减少的明显消除,如FA处理后,证明两种试剂均诱导DPC,而MMC主要诱导ICL。在不同的细胞中,诱导的交联类型和诱导的染色体损伤之间可能存在相关性。本文研究了AA、MMC和FA处理的修复缺陷突变型中国仓鼠卵巢细胞系。TCR/NER通路参与FA诱导的DPC的修复,但较少参与AA诱导的DPC的修复。我们的初步数据表明,DPC是较弱的诱导剂的SCE相比,ICLs。(C)2008 Elsevier B. V.保留所有权利。
Acetaldehyde (AA) was tested along with two other crosslinking agents: formaldehyde (FA), an inducer of DNA-protein crosslinks (DPCs) and mitomycin C (MMC), an inducer of interstrand crosslinks (ICLs), to find out whether the mechanism of action of AA resembles more MMC or FA.Using a modification of the standard protocol for comet assay we demonstrate that AA induces crosslinks, Using a combination of alkaline comet version and proteinase-K, a clear abrogation of AA-induced reduction in DNA migration, like after FA treatment, was observed demonstrating that both agents induce DPCs, whereas MMC induces predominantly ICLs.A possible correlation between the types of induced crosslink and the induction chromosome damage in different repair deficient mutant Chinese hamster ovary cell lines treated with AA, MMC and FA was investigated. TCR/NER pathways are involved in repairing FA induced DPCs, but less in AA-induced DPCs. Our preliminary data suggest that DPCs are weaker inducers of SCEs in comparison with ICLs. (C) 2008 Elsevier B.V. All rights reserved.