ArticleProceedings of the National Academy of Sciences of the United States of America2015
Intrinsic mutagenic properties of 5-chlorocytosine: A mechanistic connection between chronic inflammation and cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Psychological distress in relation to site specific cancer mortality: pooling of unpublished data from 16 prospective cohort studies.BMJ (Clinical research ed.) · 2017Pooled it
- Redox regulation: mechanisms, biology and therapeutic targets in diseases.Signal transduction and targeted therapy · 2025Review
- A role for the stringent response in ciprofloxacin resistance in Pseudomonas aeruginosa.Scientific reports · 2024Article
- 5-Chloro-2'-deoxycytidine Induces a Distinctive High-Resolution Mutational Spectrum of Transition Mutations In Vivo.Chemical research in toxicology · 2024Article
- Detrimental Actions of Chlorinated Nucleosides on the Function and Viability of Insulin-Producing Cells.International journal of molecular sciences · 2023Article
- Mesenchymal stromal cells in tumor microenvironment remodeling of BCR-ABL negative myeloproliferative diseases.Frontiers in oncology · 2023Review
- Hypochlorous Acid Chemistry in Mammalian Cells-Influence on Infection and Role in Various Pathologies.International journal of molecular sciences · 2022Review
- Hydroxyl radical is a significant player in oxidative DNA damage in vivo.Chemical Society reviews · 2021Review
- When Benign Becomes Cancer: Malignant Degeneration of Chronic Inflammation.Seminars in plastic surgery · 2021Review
- Genetic analysis of endometriosis and depression identifies shared loci and implicates causal links with gastric mucosa abnormality.Human genetics · 2021Article
- Analysis of mutations in tumor and normal adjacent tissue via fluorescence detection.Environmental and molecular mutagenesis · 2021Article
- Immune System in Action.Advances in experimental medicine and biology · 2021Article
- Psychological Distress and All-Cause, Cardiovascular Disease, Cancer Mortality Among Adults with and without Diabetes.Clinical epidemiology · 2021Article
- Structural Insights Into Tautomeric Dynamics in Nucleic Acids and in Antiviral Nucleoside Analogs.Frontiers in molecular biosciences · 2021Review
- Multi-Omics Characterization of Inflammatory Bowel Disease-Induced Hyperplasia/Dysplasia in theInternational journal of molecular sciences · 2020Article
- Inhibition of DNA methylation in proliferating human lymphoma cells by immune cell oxidants.The Journal of biological chemistry · 2020Article
- Oxidative-Antioxidant Imbalance and Impaired Glucose Metabolism in Schizophrenia.Biomolecules · 2020Review
- Lysine-Functionalized Tungsten Disulfide Quantum Dots as Artificial Enzyme Mimics for Oxidative Stress Biomarker Sensing.ACS omega · 2020Article
- Inflammation-induced DNA damage, mutations and cancer.DNA repair · 2019Review
- 8-Chloroadenosine induces apoptosis in human coronary artery endothelial cells through the activation of the unfolded protein response.Redox biology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
During chronic inflammation, neutrophil-secreted hypochlorous acid can damage nearby cells inducing the genomic accumulation of 5-chlorocytosine (5ClC), a known inflammation biomarker. Although 5ClC has been shown to promote epigenetic changes, it has been unknown heretofore if 5ClC directly perpetrates a mutagenic outcome within the cell. The present work shows that 5ClC is intrinsically mutagenic, both in vitro and, at a level of a single molecule per cell, in vivo. Using biochemical and genetic approaches, we have quantified the mutagenic and toxic properties of 5ClC, showing that this lesion caused C→T transitions at frequencies ranging from 3-9% depending on the polymerase traversing the lesion. X-ray crystallographic studies provided a molecular basis for the mutagenicity of 5ClC; a snapshot of human polymerase β replicating across a primed 5ClC-containing template uncovered 5ClC engaged in a nascent base pair with an incoming dATP analog. Accommodation of the chlorine substituent in the template major groove enabled a unique interaction between 5ClC and the incoming dATP, which would facilitate mutagenic lesion bypass. The type of mutation induced by 5ClC, the C→T transition, has been previously shown to occur in substantial amounts both in tissues under inflammatory stress and in the genomes of many inflammation-associated cancers. In fact, many sequence-specific mutational signatures uncovered in sequenced cancer genomes feature C→T mutations. Therefore, the mutagenic ability of 5ClC documented in the present study may constitute a direct functional link between chronic inflammation and the genetic changes that enable and promote malignant transformation.
Indexed as
Identifiers
What OpenQuestion holds
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.