Evidence map›Paper›PMID 21421565›Full record

ArticleNucleic acids research2011

Irreparable complex DNA double-strand breaks induce chromosome breakage in organotypic three-dimensional human lung epithelial cell culture.

Aroumougame Asaithamby, Burong Hu, Oliver Delgado, Liang-Hao Ding, Michael D Story, John D Minna, Jerry W Shay, David J Chen

Abstract read
In one paragraph

Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed.

  1. Review
  2. Framework to calculateMedical physics · 2025
    Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. miR-29b-3p Increases Radiosensitivity in Stemness Cancer CellsFrontiers in cell and developmental biology · 2021
    Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Aroumougame AsaithambyDivision of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas, Southwestern Medical Centre, Dallas, TX 75390, USA. Aroumougame.Asaithamby@UTsouthwestern.edu
Burong Hu
Oliver Delgado
Liang-Hao Ding
Michael D Story
John D Minna
Jerry W Shay
David J Chen

Funding

UNIVERSITY OF TEXAS--SPORE IN LUNG CANCERP50CA070907 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI GIBBONS, DON LYNN · 1996 to 2024
$57.4M
UT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Sandi Leigh Pruitt · 2010 to 2026
$53.7M
Functions of WRN in Response to DNA Double-Strand BreaksR01CA134991 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI CHEN, DAVID J · 2009 to 2013
$1.6M
NCI NIH HHS CA134991NCI NIH HHS P30 CA142543NCI NIH HHS P50 CA070907
6 · The paper itself

Abstract

DNA damage and consequent mutations initiate the multistep carcinogenic process. Differentiated cells have a reduced capacity to repair DNA lesions, but the biological impact of unrepaired DNA lesions in differentiated lung epithelial cells is unclear. Here, we used a novel organotypic human lung three-dimensional (3D) model to investigate the biological significance of unrepaired DNA lesions in differentiated lung epithelial cells. We showed, consistent with existing notions that the kinetics of loss of simple double-strand breaks (DSBs) were significantly reduced in organotypic 3D culture compared to kinetics of repair in two-dimensional (2D) culture. Strikingly, we found that, unlike simple DSBs, a majority of complex DNA lesions were irreparable in organotypic 3D culture. Levels of expression of multiple DNA damage repair pathway genes were significantly reduced in the organotypic 3D culture compared with those in 2D culture providing molecular evidence for the defective DNA damage repair in organotypic culture. Further, when differentiated cells with unrepaired DNA lesions re-entered the cell cycle, they manifested a spectrum of gross-chromosomal aberrations in mitosis. Our data suggest that downregulation of multiple DNA repair pathway genes in differentiated cells renders them vulnerable to DSBs, promoting genome instability that may lead to carcinogenesis.

Indexed as

Chromosome BreakageDNA Breaks, Double-StrandedCell DifferentiationCell LineChromosome AberrationsDNA RepairDown-RegulationEpithelial CellsHumansImaging, Three-DimensionalIronKineticsLinear Energy TransferLungOrgan Culture TechniquesIron

Identifiers

PMID21421565
PMCPMC3141259

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.