Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2067/48979
Titolo: The mitochondrial poison carbonyl cyanide 3-chlorophenyl hydrazone (CCCP) induces aneugenic effects in primary human fibroblasts: A possible link between mitochondrial dysfunction and chromosomal loss
Autori: Marcon, Francesca
De Battistis, Francesca
Siniscalchi, Ester
Crebelli, Riccardo
Meschini, Roberta 
Data pubblicazione: 2022
An association between proper chromosome segregation and intact mitochondria has been extensively reported. This could be related to the effects on the progression of cell division of altered energy production, increased oxidative stress, and deregulated calcium homeostasis. However, evidence for a direct relationship is still lacking. The present study was aimed at investigating the possible effect of mitochondrial dysfunction on chromosomal instability as detected in primary human cells treated with the mitochondrial poison carbonyl cyanide 3-chlorophenyl hydrazone (CCCP). Chromosome instability was analyzed in anaphase and interphase cells to follow the fate of chromosome damage during the progression of mitosis and the subsequent cell cycle. Through the combination of cytogenetic approaches and molecular analyses, i.e. morphological cell analysis, formation and characterization of micronucleus content, Comet assay, and gene expression, it was demonstrated that the prevalent DNA damage associated with CCCP treatment was the induction of chromosome loss, while primary DNA damage was not detected. No alterations in the shape of anaphase cells were observed nor induction of multipolar spindles. The proper activation of mitotic checkpoint was maintained. A linear dose-response curve characterizing the CCCP effects suggested that multiple cellular targets could be affected by the CCCP-induced mitochondrial dysfunctions triggering aneuploidy. Conversely, a steep increase was induced by the positive control vinblastine, known to have tubulin as a unique target. In addition, the effect of CCCP on mitochondrial function was demonstrated by changes in mitochondrial DNA copy number and in the expression of genes involved in mitochondrial maintenance. Overall, these results indicate that the mitochondrial poison CCCP may induce aneugenic effects.
URI: http://hdl.handle.net/2067/48979
ISSN: 02678357
DOI: 10.1093/mutage/geac008
È visualizzato nelle collezioni:A1. Articolo in rivista

File in questo documento:
File Descrizione DimensioniFormato Existing users please
Marcon et al 2022 (CCCP induces aneugenic effects in primary fibroblasts).pdfPDF disponibile su richiesta683.59 kBAdobe PDF  Richiedi una copia
Visualizza tutti i metadati del documento

Page view(s)

Last Week
Last month
controllato il 21-mar-2023

Google ScholarTM



Tutti i documenti nella community "Unitus Open Access" sono pubblicati ad accesso aperto.
Tutti i documenti nella community Prodotti della Ricerca" sono ad accesso riservato salvo diversa indicazione per alcuni documenti specifici