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Do bacterial genotoxins contribute to chronic inflammation, genomic instability and tumor progression?
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.ORCID-id: 0000-0002-1209-0942
2011 (Engelska)Ingår i: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 278, nr 23, s. 4577-4588Artikel, forskningsöversikt (Refereegranskat) Published
Abstract [en]

Cytolethal distending toxin, produced by several Gram-negative bacteria, and colibactin, secreted by several commensal and extraintestinal pathogenic Escherichia coli strains, are the first bacterial genotoxins to be described to date. Exposure to cytolethal distending toxin and colibactin induces DNA damage, and consequently activates the DNA damage response, resulting in cell cycle arrest of the intoxicated cells and DNA repair. Irreversible DNA damage will lead to cell death by apoptosis or to senescence. It is well established that chronic exposure to DNA damaging agents, either endogenous (reactive oxygen species) or exogenous (ionizing radiation), may cause genomic instability as a result of the alteration of genes coordinating the DNA damage response, thus favoring tumor initiation and progression. In this review, we summarize the state of the art of the biology of cytolethal distending toxin and colibactin, focusing on the activation of the DNA damage response and repair pathways, and discuss the cellular responses induced in intoxicated cells, as well as how prolonged intoxication may lead to chronic inflammation, the accumulation of genomic instability, and tumor progression in both in vitro and in vivo models.

Ort, förlag, år, upplaga, sidor
John Wiley & Sons, 2011. Vol. 278, nr 23, s. 4577-4588
Nationell ämneskategori
Cell- och molekylärbiologi Cellbiologi Immunologi Mikrobiologi
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URN: urn:nbn:se:umu:diva-165145DOI: 10.1111/j.1742-4658.2011.08125.xISI: 000297155900010PubMedID: 21585655OAI: oai:DiVA.org:umu-165145DiVA, id: diva2:1369412
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Tillgänglig från: 2019-11-12 Skapad: 2019-11-12 Senast uppdaterad: 2019-11-12Bibliografiskt granskad

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