ArticleChemical research in toxicology2016
Covalent DNA-Protein Cross-Linking by Phosphoramide Mustard and Nornitrogen Mustard in Human Cells.
Article in Chemical research in toxicology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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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.
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Who cites it
36 citing papers in PubMed, 64 citations in OpenAlex.
- Isotope Dilution NanoLC-MS/MS Quantitation of Methylglyoxal DNA-Protein Cross-Links: Formation and Repair in Human Cells.Analytical chemistry · 2026Article
- DNA-Protein Cross-Link Formation and Cellular Toxicity by Chimeric Bis-Electrophiles.The Journal of organic chemistry · 2026Article
- Current progress in research on ocular injury caused by exposure to vesicants.Progress in retinal and eye research · 2025Review
- Isotope Dilution nanoLC-MS/MS Quantitation of Methylglyoxal DNA-Protein Crosslinks: Formation and Repair in Human Cells.bioRxiv : the preprint server for biology · 2025Article
- Examination of a Chimeric Bis-Electrophile for Selective DNA-Protein Cross-Linking and Mechlorethamine Reveals an Unknown Source of Nitrogen Mustard Cytotoxicity.Journal of the American Chemical Society · 2025Article
- Synthetic Lethal Combinations of DNA Repair Inhibitors and Genotoxic Agents to Target High-Risk Diffuse Large B Cell Lymphoma.Hematological oncology · 2025Article
- SPRTN metalloprotease participates in repair of ROS-mediated DNA-protein crosslinks.Scientific reports · 2024Article
- Nitrogen mustard induces dynamic nuclear protein spectrum change and DNA-protein crosslinking, with p97 mediating repair.Heliyon · 2024Article
- Endogenous Cellular Metabolite Methylglyoxal Induces DNA-Protein Cross-Links in Living Cells.ACS chemical biology · 2024Article
- Quantification of Intracellular DNA-Protein Cross-Links with N7-Methyl-2'-Deoxyguanosine and Their Contribution to Cytotoxicity.Chemical research in toxicology · 2024Article
- Isolation and detection of DNA-protein crosslinks in mammalian cells.Nucleic acids research · 2024Article
- Enzymatic Processing of DNA-Protein Crosslinks.Genes · 2024Review
- Ubiquitin signaling and the proteasome drive human DNA-protein crosslink repair.Nucleic acids research · 2023Article
- Chemical RNA Cross-Linking: Mechanisms, Computational Analysis, and Biological Applications.JACS Au · 2023Review
- From vision toward best practices: EvaluatingFrontiers in toxicology · 2023Article
- Glutathione-Mediated Conjugation of Anticancer Drugs: An Overview of Reaction Mechanisms and Biological Significance for Drug Detoxification and Bioactivation.Molecules (Basel, Switzerland) · 2022Review
- Revisited Cyclophosphamide in the Treatment of Lupus Nephritis.BioMed research international · 2022Review
- Novel 4-Hydroxybenzyl Adducts in Human Hemoglobin: Structures and Mechanisms of Formation.Chemical research in toxicology · 2021Article
- Synthesis and polymerase bypass studies of DNA-peptide and DNA-protein conjugates.Methods in enzymology · 2021Article
- Cross-linking of the DNA repair protein ODNA repair · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
N,N-Bis-(2-chloroethyl)-phosphorodiamidic acid (phosphoramide mustard, PM) and N,N-bis-(2-chloroethyl)-amine (nornitrogen mustard, NOR) are the two biologically active metabolites of cyclophosphamide, a DNA alkylating drug commonly used to treat lymphomas, breast cancer, certain brain cancers, and autoimmune diseases. PM and NOR are reactive bis-electrophiles capable of cross-linking cellular biomolecules to form covalent DNA-DNA and DNA-protein cross-links (DPCs). In the present work, a mass spectrometry-based proteomics approach was employed to characterize PM- and NOR-mediated DNA-protein cross-linking in human cells. Following treatment of human fibrosarcoma cells (HT1080) with cytotoxic concentrations of PM, over 130 proteins were found to be covalently trapped to DNA, including those involved in transcriptional regulation, RNA splicing/processing, chromatin organization, and protein transport. HPLC-ESI(+)-MS/MS analysis of proteolytic digests of DPC-containing DNA from NOR-treated cells revealed a concentration-dependent formation of N-[2-[cysteinyl]ethyl]-N-[2-(guan-7-yl)ethyl]amine (Cys-NOR-N7G) conjugates, confirming that it cross-links cysteine thiols of proteins to the N7 position of guanines in DNA. Cys-NOR-N7G adduct numbers were higher in NER-deficient xeroderma pigmentosum cells (XPA) as compared with repair proficient cells. Furthermore, both XPA and FANCD2 deficient cells were sensitized to PM treatment as compared to that of wild type cells, suggesting that Fanconi anemia and nucleotide excision repair pathways are involved in the removal of cyclophosphamide-induced DNA damage.
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Registered trials
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