Effect of arsenic on telomerase and apoptosis in human keratinocytes and leukemia cells and epidermoid tumor cell line invitro
- Author Rupanwita Sarkar
- DOI 10.17605/O
- Country : India
- Subject : Zoology
Keywords : Telomerase, TERT, DMPO, Telomere, Proliferation, Cancer
Abstract
Telomeres at the chromosome ends in eukaryotic organisms is important for the maintenance of genome stability. Telomeres are noncoding, hexanucleotide repetitive sequences. It is generally active in cell-types with high replication rates, including germ and immune cells. Telomeres are critical in maintaining chromosome. Arsenic, a human carcinogen is known for it's clastogenicity. About 80-90% of various cancer cells have detectable telomerase activity, so it is a potential anticancer target. Telomerase reverse transcriptase (TERT) is a key component of telomerase. The expression of TERT is a rate-limiting factor. The mammalian protein TERT (hTRT/hEST2/TP2/TCS1) contain reverse transcriptase motifs and is associated with telomerase activity. Low concentration (0.1-1μMm HaCaT and 0.1-0.5 μMin HL-60) of arsenite increased telomerase activity, maintained telomerase length. High Concentration (>1-40μM) of arsenite decreased telomerase activity, telomere length. 5,5-dimethyl-1 pyrroline-N-Oxide (DMPO) was effective in protecting the arsenic-included telomere attrition and apoptosis. The carcinogenic effects of arsenic maybe partly attributed to increase in telomerase activity and leading to telomeric DNA attrition.
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