Evidence map›Paper›PMID 36714466›Full record

ArticleToxicology reports2023

Comparative analysis of chlorambucil-induced DNA lesion formation and repair in a spectrum of different human cell systems.

Sarah Ceylan Krassnig, Marina Mäser, Nicola Anna Probst, Jens Werner, Charlotte Schlett, Nina Schumann, Gudrun von Scheven, Aswin Mangerich, Alexander Bürkle

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Toxicology reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

6 citing papers in PubMed, 10 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

9 authors at 2 institutions in 1 country.

Sarah Ceylan KrassnigMolecular Toxicology, Department of Biology, University of Konstanz, D-78464 Konstanz, Germany.
Marina MäserMolecular Toxicology, Department of Biology, University of Konstanz, D-78464 Konstanz, Germany.
Nicola Anna ProbstMolecular Toxicology, Department of Biology, University of Konstanz, D-78464 Konstanz, Germany.
Jens WernerMolecular Toxicology, Department of Biology, University of Konstanz, D-78464 Konstanz, Germany.
Charlotte SchlettMolecular Toxicology, Department of Biology, University of Konstanz, D-78464 Konstanz, Germany.
Nina SchumannMolecular Toxicology, Department of Biology, University of Konstanz, D-78464 Konstanz, Germany.
Gudrun von SchevenMolecular Toxicology, Department of Biology, University of Konstanz, D-78464 Konstanz, Germany.
Aswin MangerichMolecular Toxicology, Department of Biology, University of Konstanz, D-78464 Konstanz, Germany.
Alexander BürkleMolecular Toxicology, Department of Biology, University of Konstanz, D-78464 Konstanz, Germany.
University of Konstanz · DEUniversity of Potsdam · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chlorambucil (CLB) belongs to the class of nitrogen mustards (NMs), which are highly reactive bifunctional alkylating agents and were the first chemotherapeutic agents developed. They form DNA interstrand crosslinks (ICLs), which cause a blockage of DNA strand separation, inhibiting essential processes in DNA metabolism like replication and transcription. In fast replicating cells, e.g., tumor cells, this can induce cell death. The upregulation of ICL repair is thought to be a key factor for the resistance of tumor cells to ICL-inducing cytostatic agents including NMs. To monitor induction and repair of CLB-induced ICLs, we adjusted the automated reversed fluorometric analysis of alkaline DNA unwinding assay (rFADU) for the detection of ICLs in adherent cells. For the detection of monoalkylated DNA bases we established an LC-MS/MS method. We performed a comparative analysis of adduct formation and removal in five human cell lines and in peripheral blood mononuclear cells (PBMCs) after treatment with CLB. Dose-dependent increases in adduct formation were observed, and suitable treatment concentrations were identified for each cell line, which were then used for monitoring the kinetics of adduct formation. We observed significant differences in the repair kinetics of the cell lines tested. For example, in A2780 cells, hTERT immortalized VH10 cells, and in PBMCs a time-dependent repair of the two main monoalkylated DNA-adducts was confirmed. Regarding ICLs, repair was observed in all cell systems except for PBMCs. In conclusion, LC-MS/MS analyses combined with the rFADU technique are powerful tools to study the molecular mechanisms of NM-induced DNA damage and repair. By applying these methods to a spectrum of human cell systems of different origin and transformation status, we obtained insight into the cell-type specific repair of different CLB-induced DNA lesions, which may help identify novel resistance mechanisms of tumors and define molecular targets for therapeutic interventions.

Indexed as

BER, base excision repairChlorambucilCLB, chlorambucildG, 2'-deoxyguanosineDNA repair kineticshTERT, human telomerase reverse transcriptaseICL, interstrand crosslinkInterstrand crosslinkMass spectrometryMonoalkylated DNA adductsMS, mass spectrometryNER, nucleotide excision repairNitrogen mustardNM, Nitrogen mustardPBMCs, peripheral blood mononuclear cellsPI, propidium iodiderFADU, reverse fluorometric analysis of alkaline DNA unwindingRPE-1, human retinal pigment epithelialSD, standard deviationVH10, human foreskin fibroblasts

Identifiers

PMID36714466
PMCPMC9881385
OpenAlexW4317569474

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.