In vivo and in vitro inhibitory effects of acrylamide on DNA topoisomerase II

Giulia Sciandrello, Irene Catanzaro, Fabio Caradonna, Giuseppa Barbata, Maurizio Mauro

Risultato della ricerca: Conference contribution

Abstract

Acrylamide (AA), a chemical produced in several foodstuffs when cooked at a high temperature, isconsidered a probable human carcinogen, but the molecular mechanism underlying its genotoxicityhas not fully known. Numerous authors have reported the induction by AA of DNA double strandbreaks and sister chromatid exchange (SCE); we here confirmed the acrylamide capability ofdamaging DNA by utilizing Comet assay, which showed a dose-dependent increase of tail lenght, inmetabolically non competent V79 Chinese hamster cells.Moreover, we observed that Acrylamide (AA) was able to antagonize in vivo the citotoxicity of wellknow poison etoposide; this suggested that topoisomerase II activity was affected by AA. Thehypothesis was confirmed in in vitro tests: we observed, in fact, a strong inhibitory effect of AAagainst topoisomerase II in the kDNA assay and in topoisomerase II-mediated supercoiled DNArelaxation assay. In particular, this latter inhibition was not accompanied by stabilization of acovalent topoisomerase II-DNA intermediate. In order to characterize AA target(s), we pretreatedpBR322 with AA and observed that this substrate became quickly incompetent in the topoisomeraseII catalytic assay. These results suggest that DNA could be a target for Acrylamide-inducedinhibition of topoisomerase II.Furthermore, preliminary results seem to indicate the possibility that another mode of action ofacrylamide is related to its affinity for topoisomerase II sulphydryl groups, according to recentevidences reporting that thiol-reactive compounds can induce DNA damage through a nongenotoxicmechanism, such as the thiolation of the nuclear protein topoisomerase II.
Lingua originaleEnglish
Titolo della pubblicazione ospitePubblicazione on line degli atti del IV Congresso Dip. Biologia Cellulare e dello Sviluppo dell'Università di Palermo
Numero di pagine1
Stato di pubblicazionePublished - 2006

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