title: Role of the antioxidant defence system and telomerase in arsenic-induced genomic instability.
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 SOD1expression 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 SOD1and high levels of ROS acquired a transformed phenotype. Treatment with 5-azacytidine determined an increase of SOD1expression in a clone and decrease in one other, suggesting that aberrant DNA methylation may be responsible for the abnormal expression of SOD1or SOD1inhibitor genes in different clones. TRAP assay results 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 arsenite-induced death perpetuated the memory of past exposure via ROS likely because antioxidant and telomerase activity impairment and ultimately acquire a transformed phenotype.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Sezione di Biologia cellulare, Università di Palermo, Viale delle Scienze, Edificio 16 - 90128 Palermo, Italy. fabio.caradonna@unipa.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Caradonna
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Sezione di Biologia cellulare, Università di Palermo, Viale delle Scienze, Edificio 16 - 90128 Palermo, Italy.|Present address: Albert Einstein College of Medicine, Department of Obstetrics & Gynecology and Women's Health, Michael F. Price Center, 1301 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Mauro
mesh_terms: D000818:Animals; D000975:Antioxidants; D018053:Arsenites / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D003412:Cricetulus / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D042822:Genomic Instability / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000187:drug effects* / Q000235:genetics
chemical_list: D000975:Antioxidants; D018053:Arsenites; D017382:Reactive Oxygen Species; D002374:Catalase; D013482:Superoxide Dismutase; D019098:Telomerase; C015001:arsenite