ArticleOncogene2000
Homologous recombination as a potential target for caffeine radiosensitization in mammalian cells: reduced caffeine radiosensitization in XRCC2 and XRCC3 mutants.
Article in Oncogene, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.
What it found
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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.
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
34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 98 citations in OpenAlex.
- Dose-response meta-analysis of coffee consumption and risk of colorectal adenoma.European journal of clinical nutrition · 2020Pooled it
- Consumption of coffee associated with reduced risk of liver cancer: a meta-analysis.BMC gastroenterology · 2013Pooled it
- Article
- Pleiotropic Effects of Caffeine Leading to Chromosome Instability and Cytotoxicity in Eukaryotic Microorganisms.Journal of microbiology and biotechnology · 2021Review
- Dietary Acrylamide Intake and the Risk of Liver Cancer: The Japan Public Health Center-Based Prospective Study.Nutrients · 2020Article
- The association between coffee consumption and bladder cancer in the bladder cancer epidemiology and nutritional determinants (BLEND) international pooled study.Cancer causes & control : CCC · 2019Article
- Scientific Opinion on Flavouring Group Evaluation 49, Revision 1 (FGE.49Rev1): xanthine alkaloids from the priority list.EFSA journal. European Food Safety Authority · 2017Article
- Coffee and cancer risk: A meta-analysis of prospective observational studies.Scientific reports · 2016Article
- Caffeine inhibits gene conversion by displacing Rad51 from ssDNA.Nucleic acids research · 2015Article
- Caffeine impairs resection during DNA break repair by reducing the levels of nucleases Sae2 and Dna2.Nucleic acids research · 2015Article
- Article
- Concurrent inhibition of enzymatic activity and NF-Y-mediated transcription of Topoisomerase-IIα by bis-DemethoxyCurcumin in cancer cells.Cell death & disease · 2013Article
- The kinase activity of ataxia-telangiectasia mutated interferes with adenovirus E4 mutant DNA replication.Journal of virology · 2013Article
- Caffeine suppresses homologous recombination through interference with RAD51-mediated joint molecule formation.Nucleic acids research · 2013Article
- DNA double-strand break repair as determinant of cellular radiosensitivity to killing and target in radiation therapy.Frontiers in oncology · 2013Article
- Chemoprevention against hepatocellular carcinoma.Clinical journal of gastroenterology · 2011Article
- p53-dependent G(1) arrest in 1st or 2nd cell cycle may protect human cancer cells from cell death after treatment with ionizing radiation and Chk1 inhibitors.Cell proliferation · 2010Article
- Review
- Gamma-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin.Nucleic acids research · 2008Review
- Caffeine markedly sensitizes human mesothelioma cell lines to pemetrexed.Cancer chemotherapy and pharmacology · 2008Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The radiosensitizing effect of caffeine has been associated with the disruption of multiple DNA damage-responsive cell cycle checkpoints, but several lines of evidence also implicate inhibition of DNA repair. The role of DNA repair inhibition in caffeine radiosensitization remains uncharacterized, and it is unknown which repair process, or lesion, is affected. We show that a radiosensitive cell line, mutant for the RAD51 homolog XRCC2 and defective in homologous recombination repair (HRR), displays significantly diminished caffeine radiosensitization that can be restored by expression of XRCC2. Despite the reduced radiosensitization, caffeine effectively abrogates checkpoints in S and G2 phases in XRCC2 mutant cells indicating that checkpoint abrogation is not sufficient for radiosensitization. Another radiosensitive line, mutant for XRCC3 and defective in HRR, similarly shows reduced caffeine radiosensitization. On the other hand, a radiosensitive mutant (irs-20) of DNA-PKcs with a defect in non-homologous end-joining (NHEJ) is radiosensitized by caffeine to an extent comparable to wild-type cells. In addition, rejoining of radiation-induced DNA DSBs, that mainly reflects NHEJ, remains unaffected by caffeine in XRCC2 and XRCC3 mutants, or their wild-type counterparts. These observations suggest that caffeine targets steps in HRR but not in NHEJ and that abrogation of checkpoint response is not sufficient to explain radiosensitization. Indeed, immortalized fibroblasts from AT patients show caffeine radiosensitization despite the checkpoint defects associated with ATM mutation. We propose that caffeine radiosensitization is mediated by inhibition of stages in DNA DSB repair requiring HRR and that checkpoint disruption contributes by allowing these DSBs to transit into irreparable states. Thus, checkpoints may contribute to genomic stability by promoting error-free HRR.
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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.