Relationship between DNA lesions, DNA repair and chromosomal damage induced by acetaldehyde.
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.
Lorenti Garcia
Claudia
C
Department of Agrobiology and Agrochemistry, University of Tuscia, Via S. C. De Lellis snc, I-01100 Viterbo, Italy.
Mechilli
Manuela
M
Proietti De Santis
Luca
L
Schinoppi
Angelo
A
Kobos
Katarzyna
K
Palitti
Fabrizio
F
D000079:Acetaldehyde / Q000633:toxicity*; D000818:Animals; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects; D002869:Chromosome Aberrations / Q000187:drug effects*; D033481:Chromosomes, Mammalian / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D019286:Endopeptidase K / Q000378:metabolism; D005557:Formaldehyde / Q000633:toxicity; D008940:Mitotic Index; D012854:Sister Chromatid Exchange / Q000187:drug effects
D003432:Cross-Linking Reagents; D005557:Formaldehyde; D004247:DNA; D019286:Endopeptidase K; D000079:Acetaldehyde