Short dysfunctional telomeres impair the repair of arsenite-induced oxidative damage in mouse cells

Jennifer P.A. Newman, Birendranath Banerjee, Wanru Fang, Anuradha Poonepalli, Lakshmidevi Balakrishnan, Grace Kah Mun Low, Rabindra N. Bhattacharjee, Shizuo Akira, Manikandan Jayapal, Alirio J. Melendez, Rajamanickam Baskar, Han Woong Lee, M. Prakash Hande

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Telomeres and telomerase appear to participate in the repair of broken DNA ends produced by oxidative damage. Arsenite is an environmental contaminant and a potent human carcinogen, which induces oxidative stress on cells via the generation of reactive oxygen species affecting cell viability and chromosome stability. It promotes telomere attrition and reduces cell survival by apoptosis. In this study, we used mouse embryonic fibroblasts (MEFs) from mice lacking telomerase RNA component (mTERC-/- mice) with long (early passage or EP) and short (late passage or LP) telomeres to investigate the extent of oxidative damage by comparing the differences in DNA damage, chromosome instability, and cell survival at 24 and 48 h of exposure to sodium arsenite (As3+; NaAsO2). There was significantly high level of DNA damage in mTERC-/- cells with short telomeres as determined by alkaline comet assay. Consistent with elevated DNA damage, increased micronuclei (MN) induction reflecting gross genomic instability was also observed. Fluorescence in situ hybridization (FISH) analysis revealed that increasing doses of arsenite augmented the chromosome aberrations, which contributes to genomic instability leading to possibly apoptotic cell death and cell cycle arrest. Microarray analysis has revealed that As3+ treatment altered the expression of 456 genes of which 20% of them have known functions in cell cycle and DNA damage signaling and response, cell growth, and/or maintenance. Results from our studies imply that short dysfunctional telomeres impair the repair of oxidative damage caused by arsenite. The results will have implications in risk estimation as well as cancer chemotherapy.

Original languageEnglish
Pages (from-to)796-809
Number of pages14
JournalJournal of Cellular Physiology
Volume214
Issue number3
DOIs
Publication statusPublished - 2008 Mar 1

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Telomere
Repair
Cells
DNA Damage
Chromosomes
DNA
Cell Survival
Chromosomal Instability
Genomic Instability
Oxidative stress
Comet Assay
Chemotherapy
Telomerase
Cell growth
Cell death
Fibroblasts
Microarray Analysis
Microarrays
Cell Cycle Checkpoints
Aberrations

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Newman, J. P. A., Banerjee, B., Fang, W., Poonepalli, A., Balakrishnan, L., Low, G. K. M., ... Hande, M. P. (2008). Short dysfunctional telomeres impair the repair of arsenite-induced oxidative damage in mouse cells. Journal of Cellular Physiology, 214(3), 796-809. https://doi.org/10.1002/jcp.21276
Newman, Jennifer P.A. ; Banerjee, Birendranath ; Fang, Wanru ; Poonepalli, Anuradha ; Balakrishnan, Lakshmidevi ; Low, Grace Kah Mun ; Bhattacharjee, Rabindra N. ; Akira, Shizuo ; Jayapal, Manikandan ; Melendez, Alirio J. ; Baskar, Rajamanickam ; Lee, Han Woong ; Hande, M. Prakash. / Short dysfunctional telomeres impair the repair of arsenite-induced oxidative damage in mouse cells. In: Journal of Cellular Physiology. 2008 ; Vol. 214, No. 3. pp. 796-809.
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Newman, JPA, Banerjee, B, Fang, W, Poonepalli, A, Balakrishnan, L, Low, GKM, Bhattacharjee, RN, Akira, S, Jayapal, M, Melendez, AJ, Baskar, R, Lee, HW & Hande, MP 2008, 'Short dysfunctional telomeres impair the repair of arsenite-induced oxidative damage in mouse cells', Journal of Cellular Physiology, vol. 214, no. 3, pp. 796-809. https://doi.org/10.1002/jcp.21276

Short dysfunctional telomeres impair the repair of arsenite-induced oxidative damage in mouse cells. / Newman, Jennifer P.A.; Banerjee, Birendranath; Fang, Wanru; Poonepalli, Anuradha; Balakrishnan, Lakshmidevi; Low, Grace Kah Mun; Bhattacharjee, Rabindra N.; Akira, Shizuo; Jayapal, Manikandan; Melendez, Alirio J.; Baskar, Rajamanickam; Lee, Han Woong; Hande, M. Prakash.

In: Journal of Cellular Physiology, Vol. 214, No. 3, 01.03.2008, p. 796-809.

Research output: Contribution to journalArticle

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AU - Balakrishnan, Lakshmidevi

AU - Low, Grace Kah Mun

AU - Bhattacharjee, Rabindra N.

AU - Akira, Shizuo

AU - Jayapal, Manikandan

AU - Melendez, Alirio J.

AU - Baskar, Rajamanickam

AU - Lee, Han Woong

AU - Hande, M. Prakash

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Newman JPA, Banerjee B, Fang W, Poonepalli A, Balakrishnan L, Low GKM et al. Short dysfunctional telomeres impair the repair of arsenite-induced oxidative damage in mouse cells. Journal of Cellular Physiology. 2008 Mar 1;214(3):796-809. https://doi.org/10.1002/jcp.21276