Lorenti Garcia Claudia, Mechilli Manuela, Proietti De Santis Luca, Schinoppi Angelo, Kobos Katarzyna, Palitti Fabrizio
Department of Agrobiology and Agrochemistry, University of Tuscia, Via S. C. De Lellis snc, I-01100 Viterbo, Italy.
Mutat Res. 2009 Mar 9;662(1-2):3-9. doi: 10.1016/j.mrfmmm.2008.11.008. Epub 2008 Nov 25.
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.
对乙醛（AA）以及另外两种交联剂进行了测试：甲醛（FA），一种DNA-蛋白质交联（DPC）诱导剂；丝裂霉素C（MMC），一种链间交联（ICL）诱导剂，以确定AA的作用机制更类似于MMC还是FA。通过对彗星试验的标准方案进行修改，我们证明AA能诱导交联。使用碱性彗星试验版本和蛋白酶K的组合，观察到与FA处理后一样，AA诱导的DNA迁移减少明显消除，这表明这两种试剂都能诱导DPC，而MMC主要诱导ICL。研究了在不同修复缺陷的突变中国仓鼠卵巢细胞系中，用AA、MMC和FA处理后，诱导的交联类型与诱导染色体损伤之间可能的相关性。TCR/NER途径参与修复FA诱导的DPC，但在AA诱导的DPC中作用较小。我们的初步数据表明，与ICL相比，DPC是较弱的姐妹染色单体交换诱导剂。
