Evidence map›Paper›PMID 33498964›Full record

ArticleInternational journal of molecular sciences2021

Genomic Adaption and Mutational Patterns in a HaCaT Subline Resistant to Alkylating Agents and Ionizing Radiation.

Reinhard Ullmann, Benjamin Valentin Becker, Simone Rothmiller, Annette Schmidt, Horst Thiermann, Hanns Leonhard Kaatsch, Gerrit Schrock, Jessica Müller, Julia Jakobi, Richard Obermair and 2 more

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 53% 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.

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

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. Article
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

12 authors at 3 institutions in 1 country.

Reinhard UllmannBundeswehr Institute of Radiobiology Affiliated to the University of Ulm, Neuherbergstr. 11, D-80937 Munich, Germany.
Benjamin Valentin BeckerBundeswehr Central Hospital, Department of Radiology and Neuroradiology, Rübenacherstrasse 170, D-56072 Koblenz, Germany.ORCID 0000-0002-8557-8797
Simone RothmillerBundeswehr Institute of Pharmacology and Toxicology, Neuherbergstr. 11, D-80937 Munich, Germany.
Annette SchmidtBundeswehr Institute of Pharmacology and Toxicology, Neuherbergstr. 11, D-80937 Munich, Germany.
Horst ThiermannBundeswehr Institute of Pharmacology and Toxicology, Neuherbergstr. 11, D-80937 Munich, Germany.
Hanns Leonhard KaatschBundeswehr Institute of Radiobiology Affiliated to the University of Ulm, Neuherbergstr. 11, D-80937 Munich, Germany.ORCID 0000-0002-6208-3425
Gerrit SchrockBundeswehr Institute of Radiobiology Affiliated to the University of Ulm, Neuherbergstr. 11, D-80937 Munich, Germany.
Jessica MüllerBundeswehr Institute of Radiobiology Affiliated to the University of Ulm, Neuherbergstr. 11, D-80937 Munich, Germany.
Julia JakobiBundeswehr Institute of Radiobiology Affiliated to the University of Ulm, Neuherbergstr. 11, D-80937 Munich, Germany.
Richard ObermairBundeswehr Institute of Radiobiology Affiliated to the University of Ulm, Neuherbergstr. 11, D-80937 Munich, Germany.
Matthias PortBundeswehr Institute of Radiobiology Affiliated to the University of Ulm, Neuherbergstr. 11, D-80937 Munich, Germany.
Harry ScherthanBundeswehr Institute of Radiobiology Affiliated to the University of Ulm, Neuherbergstr. 11, D-80937 Munich, Germany.
Universität Ulm · DEUniversität der Bundeswehr München · DEBundeswehrzentralkrankenhaus Koblenz · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sulfur mustard (SM) is a chemical warfare agent that can damage DNA via alkylation and oxidative stress. Because of its genotoxicity, SM is cancerogenic and the progenitor of many chemotherapeutics. Previously, we developed an SM-resistant cell line via chronic exposure of the popular keratinocyte cell line HaCaT to increasing doses of SM over a period of 40 months. In this study, we compared the genomic landscape of the SM-resistant cell line HaCaT/SM to its sensitive parental line HaCaT in order to gain insights into genetic changes associated with continuous alkylation and oxidative stress. We established chromosome numbers by cytogenetics, analyzed DNA copy number changes by means of array Comparative Genomic Hybridization (array CGH), employed the genome-wide chromosome conformation capture technique Hi-C to detect chromosomal translocations, and derived mutational signatures by whole-genome sequencing. We observed that chronic SM exposure eliminated the initially prevailing hypotetraploid cell population in favor of a hyperdiploid one, which contrasts with previous observations that link polyploidization to increased tolerance and adaptability toward genotoxic stress. Furthermore, we observed an accumulation of chromosomal translocations, frequently flanked by DNA copy number changes, which indicates a high rate of DNA double-strand breaks and their misrepair. HaCaT/SM-specific single-nucleotide variants showed enrichment of C > A and T > A transversions and a lower rate of deaminated cytosines in the CpG dinucleotide context. Given the frequent use of HaCaT in toxicology, this study provides a valuable data source with respect to the original genotype of HaCaT and the mutational signatures associated with chronic alkylation and oxidative stress.

Indexed as

DNA DamageMutationRadiation, IonizingAlkylating AgentsCell LineChromosome AberrationsComparative Genomic HybridizationDNADNA AdductsDNA Breaks, Double-StrandedHumansKeratinocytesMustard GasOxidative StressAlkylating AgentsDNADNA AdductsMustard Gaschronic exposureDNA alkylationgenome rearrangementsHaCaTirradiationmutational signaturesoxidative stressresistancesulfur mustard

Identifiers

PMID33498964
PMCPMC7865644
OpenAlexW3123419050

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.