Role of the antioxidant defence system and telomerase in arsenic-induced genomic instability

Fabio Caradonna, Maurizio Mauro, Maurizio Mauro

Risultato della ricerca: Article

10 Citazioni (Scopus)

Abstract

Arsenic (AS) is a reactive oxygen species (ROS)-inducer carcinogen, whose mode of action is still unclear. To defend against ROS, cells use enzymatic and non-enzymatic antioxidants, such as superoxide dismutase (SOD) and catalase. Failure of antioxidant systems (AXS) can result in dicentric chromosomes formation as well as telomere associations for the reduced activity of telomerase. In order to clarify the long-term effects of a past AS exposure, we evaluated the efficiency of the AXS and the telomerase activity in the progeny of arsenite-treated cells named ASO (arsenic shake-off) cells, previously obtained from arsenite-treated V79 cells and selected by shake-off. Despite SOD1 expression level correlated to the level of ROS observed over time, no changes of the relative amount of antioxidant activities were observed in ASO cells. Moreover, we found that clones characterised by low levels of SOD1 and high levels of ROS acquired a transformed phenotype. Treatment with 5-azacytidine determined an increase of SOD1 expression in a clone and decrease in one other, suggesting that aberrant DNA methylation may be responsible for the abnormal expression of SOD1 or SOD1 inhibitor genes in different clones. TRAP assayresults showed that the progeny of arsenite-treated cells were characterised by a time-dependent decrease of telomerase activity. Integrated results suggest that the increases of ROS levels are accompanied by defective telomerase activity. Finally, we propose that cells escaping the arseniteinduced death perpetuated the memory of past exposure via ROS likely because antioxidant and telomerase activity impairment and ultimately acquire a transformed phenotype.
Lingua originaleEnglish
pagine (da-a)1-7
Numero di pagine7
RivistaMutagenesis
Stato di pubblicazionePublished - 2016

All Science Journal Classification (ASJC) codes

  • Genetics
  • Toxicology
  • Genetics(clinical)
  • Health, Toxicology and Mutagenesis

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