+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

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



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



Mutagenesis 31(6): 661-667



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 SOD 1 or SOD1 inhibitor 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.

(PDF emailed within 0-6 h: $19.90)

Accession: 058791244

Download citation: RISBibTeXText

PMID: 27470698

DOI: 10.1093/mutage/gew034


Related references

Arsenic inhibition of telomerase transcription leads to genomic instability. Proceedings of the American Association for Cancer Research Annual Meeting 43: 1032, March, 2002

Role of genomic instability in arsenic-induced carcinogenicity. A review. Environment International 53: 29-40, 2013

Impairment of the telomere/telomerase system and genomic instability are associated with keratinocyte immortalization induced by the skin human papillomavirus type 38. Faseb Journal 22(2): 622-632, 2007

Silicon mediates arsenic tolerance in rice Oryza sativa L through lowering of arsenic uptake and improved antioxidant defence system. Ecological Engineering 52: 96-103, 2013

Role of telomeres and telomerase in genomic instability, senescence. 2007

Modulation of antioxidant defence system for arsenic detoxification in Indian mustard. Ecotoxicology and Environmental Safety 72(2): 626-634, 2008

Impairment of the telomere/telomerase system and genomic instability human papillomavirus type 38. 2008

The role of lipid peroxidation and antioxidant defence system of the kidneys in the predisposition to gentamicin-induced nephrotoxicity in rabbits. Eksperimental'naia i Klinicheskaia Farmakologiia 69(1): 33-37, 2006

Dysfunctional telomeres promote genomic instability and metastasis in the absence of telomerase activity in oncogene induced mammary cancer. Molecular Carcinogenesis 52(2): 103-117, 2013

The food supplement coenzyme Q10 and suppression of antitubercular drug-induced hepatic injury in rats: the role of antioxidant defence system, anti-inflammatory cytokine IL-10. Cell Biology and Toxicology 31(4-5): 211-219, 2016

Modulatory influence of arecanut on antioxidant 2(3)-tert-butyl-4-hydroxy anisole-induced hepatic detoxification system and antioxidant defence mechanism in mice. Cancer Letters 91(1): 107-114, 1995

Dysregulation of DNA methylation induced by past arsenic treatment causes persistent genomic instability in mammalian cells. Environmental and Molecular Mutagenesis 57(2): 137-150, 2016

The effects of smoking on antioxidant defence system and membrane free fatty acid content of erythrocytes and plasma lipid parameters: protective role of antioxidant vitamins. Nutrition Research 17(6): 931-940, 1997

The role of the peroxiredoxin Q in the antioxidant defence system of the chloroplast. Free Radical Research 37(Supplement 2): 40, 2003

Genomic instability induced by 50Hz magnetic fields is a dynamically evolving process not blocked by antioxidant treatment. Mutation Research. Genetic Toxicology and Environmental Mutagenesis 794: 46-51, 2016