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Cited by 197Telomeres, Telomerase, and SenescenceCarcinogens and Genotoxicity AssessmentDNA Repair Mechanisms

Oxidative Stress Induces Persistent Telomeric DNA Damage Responsible for Nuclear Morphology Change in Mammalian Cells

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Coluzzi, Elisa, Colamartino, Monica, Cozzi, Renata, Leone, Stefano, Meneghini, Carlo, O’Callaghan, Nathan, Sgura, Antonella·2014·PLoS ONE
DOI 10.1371/journal.pone.0110963PMC PMC4212976
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Abstract

One main function of telomeres is to maintain chromosome and genome stability. The rate of telomere shortening can be accelerated significantly by chemical and physical environmental agents. Reactive oxygen species are a source of oxidative stress and can produce modified bases (mainly 8-oxoG) and single strand breaks anywhere in the genome. The high incidence of guanine residues in telomeric DNA sequences makes the telomere a preferred target for oxidative damage. Our aim in this work is to evaluate whether chromosome instability induced by oxidative stress is related specifically to telomeric damage. We treated human primary fibroblasts (MRC-5) in vitro with hydrogen peroxide (100 and 200 µM) for 1 hr and collected data at several time points. To evaluate the persistence of oxidative stress-induced DNA damage up to 24 hrs after treatment, we analysed telomeric and genomic oxidative damage by qPCR and a modified comet assay, respectively. The results demonstrate that the genomic damage is completely repaired, while the telomeric oxidative damage persists. The analysis of telomere length reveals a significant telomere shortening 48 hrs after treatment, leading us to hypothesise that residual telomere damage could be responsible for the telomere shortening observed. Considering the influence of telomere length modulation on genomic stability, we quantified abnormal nuclear morphologies (Nucleoplasmic Bridges, Nuclear Buds and Micronuclei) and observed an increase of chromosome instability in the same time frame as telomere shortening. At subsequent times (72 and 96 hrs), we observed a restoration of telomere length and a reduction of chromosome instability, leaving us to conjecture a correlation between telomere shortening/dysfunction and chromosome instability. We can conclude that oxidative base damage leads to abnormal nuclear morphologies and that telomere dysfunction is an important contributor to this effect.

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  • Oxidative and inflammatory stress can damage telomeric DNA and alter mitochondrial function, while mitochondrial reactive oxygen species may further affect telomere maintenance.

    “Oxidative and inflammatory stress can damage telomeric DNA and alter mitochondrial function, while mitochondrial reactive oxygen species may further affect telomere maintenance [128,129,130].”

    From Placental Pathophysiology and Developmental Programming of Adult Cardiometabolic Risk: A Narrative Review of Pregnancy Exposures (2026) · cites this paper as [128]

    The Discussion says oxidative stress damages telomeres and reports accelerated telomere shortening in cells with mitochondrial DNA mutations associated with increased reactive oxygen species. The Introduction also describes oxidative damage to telomeric DNA. These passages do not establish that inflammatory stress damages telomeres or that oxidative and inflammatory stress alter mitochondrial function. (LLM, conf=0.86)

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Sorted by citations

Authors
Coluzzi, E., Colamartino, M., Cozzi, R., Leone, S., Meneghini, C., O’Callaghan, N., & Sgura, A.
Affiliations
  • Roma Tre University (IT)
  • Commonwealth Scientific and Industrial Research Organisation (AU)
Corresponding author
Sgura, Antonella
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2014-10-29
Volume
9
Issue
10
Pages
e110963
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0110963
PMC
PMC4212976
OpenAlex
W2035144476
Cited by
197
References
13
Citations by year
2026: 10 · 2025: 16 · 2024: 16 · 2023: 16 · 2022: 21 · 2021: 22 · 2020: 19 · 2019: 22 · 2018: 18 · 2017: 14 · 2016: 10 · 2015: 13
FWCI
8.22
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Iris (Roma Tre University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Keywords
oxidative stress, telomeres, telomere shortening, telomere dysfunction, chromosomal instability, 8-oxoguanine, oxidative DNA damage, hydrogen peroxide, nuclear morphology, micronuclei, nuclear buds, nucleoplasmic bridges, telomere length, fibroblasts, DNA repair
MeSH terms
Cell Line, Cell Nucleus, DNA Damage, Humans, Hydrogen Peroxide, Telomere, Oxidative Stress, Chromosomal Instability, Telomere Shortening

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