Evidence map›Paper›PMID 24732344›Full record

ArticleMutation research

Activation of DNA damage repair pathways in response to nitrogen mustard-induced DNA damage and toxicity in skin keratinocytes.

Swetha Inturi, Neera Tewari-Singh, Chapla Agarwal, Carl W White, Rajesh Agarwal

Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in Mutation research. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06421571 (A Greek, Prospective Non-interventional Study Investigating the Effectiveness and the Mechanism of Action of Chlormethine), which is not on this map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
7.5field-weighted citation impact, top 3% of its field
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.

NCT06421571 unknown statusnot on this map

A Greek, Prospective Non-interventional Study Investigating the Effectiveness and the Mechanism of Action of Chlormethine (CL) Gel in the Treatment of MF-CTCL Adult Patients

TypeobservationalSponsorNational and Kapodistrian University of AthensRan2023 to 2025Enrolled40ConditionsMycosis Fungoides
3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 36 citations in OpenAlex.

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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

5 authors at 2 institutions in 1 country.

Swetha InturiDepartment of Pharmaceutical Sciences, University of Colorado Anchutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045, USA.
Neera Tewari-SinghDepartment of Pharmaceutical Sciences, University of Colorado Anchutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045, USA.
Chapla AgarwalDepartment of Pharmaceutical Sciences, University of Colorado Anchutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045, USA.
Carl W WhiteDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Rajesh AgarwalDepartment of Pharmaceutical Sciences, University of Colorado Anchutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045, USA. Electronic address: Rajesh.Agarwal@ucdenver.edu.
University of Montana · USUniversity of Colorado Anschutz Medical Campus · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Thiols in sulfur mustard toxicityU54ES015678 · NIEHS · UNIVERSITY OF COLORADO DENVER · PI WHITE, CARL W · 2006 to 2015
$20.5M
NCI NIH HHS P30 CA046934NIEHS NIH HHS U54 ES015678NIEHS NIH HHS U54ES-015678
6 · The paper itself

Abstract

Nitrogen mustard (NM), a structural analog of chemical warfare agent sulfur mustard (SM), forms adducts and crosslinks with DNA, RNA and proteins. Here we studied the mechanism of NM-induced skin toxicity in response to double strand breaks (DSBs) resulting in cell cycle arrest to facilitate DNA repair, as a model for developing countermeasures against vesicant-induced skin injuries. NM exposure of mouse epidermal JB6 cells decreased cell growth and caused S-phase arrest. Consistent with these biological outcomes, NM exposure also increased comet tail extent moment and the levels of DNA DSB repair molecules phospho H2A.X Ser139 and p53 Ser15 indicating NM-induced DNA DSBs. Since DNA DSB repair occurs via non homologous end joining pathway (NHEJ) or homologous recombination repair (HRR) pathways, next we studied these two pathways and noted their activation as defined by an increase in phospho- and total DNA-PK levels, and the formation of Rad51 foci, respectively. To further analyze the role of these pathways in the cellular response to NM-induced cytotoxicity, NHEJ and HRR were inhibited by DNA-PK inhibitor NU7026 and Rad51 inhibitor BO2, respectively. Inhibition of NHEJ did not sensitize cells to NM-induced decrease in cell growth and cell cycle arrest. However, inhibition of the HRR pathway caused a significant increase in cell death, and prolonged G2M arrest following NM exposure. Together, our findings, indicating that HRR is the key pathway involved in the repair of NM-induced DNA DSBs, could be useful in developing new therapeutic strategies against vesicant-induced skin injury.

Indexed as

DNA DamageAnimalsBoron CompoundsCell LineChemical Warfare AgentsChromonesDNA-Activated Protein KinaseDNA-Binding ProteinsDNA RepairG2 Phase Cell Cycle CheckpointsHistonesKeratinocytesMechlorethamineMiceMorpholinesNuclear Proteins2-(morpholin-4-yl)benzo(h)chromen-4-oneBoron Compoundsboron oxideChemical Warfare AgentsChromonesDNA-Activated Protein KinaseDNA-Binding Proteinsgamma-H2AX protein, mouseHistonesMechlorethamineMorpholinesNuclear ProteinsPrkdc protein, mouseRad51 protein, mouseRad51 RecombinaseTumor Suppressor Protein p53BO2DNA double strand break (DSB) repairHRRNHEJNitrogen mustardNU7026Rad51 inhibitor

Identifiers

PMID24732344
PMCPMC4199943
OpenAlexW2029544197

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.