TAILIEUCHUNG - Báo cáo khoa học: Do bacterial genotoxins contribute to chronic inflammation, genomic instability and tumor progression?

Cytolethal distending toxin, produced by several Gram-negative bacteria, and colibactin, secreted by several commensal and extraintestinal patho-genic Escherichia coli strains, are the first bacterial genotoxins to be described to date. | fFEBS Journal REVIEW ARTICLE Do bacterial genotoxins contribute to chronic inflammation genomic instability and tumor progression Lina Guerra Riccardo Guidi and Teresa Frisan Department of Celland Molecular Biology Karolinska Institutet Stockholm Sweden Keywords bacterialgenotoxin chronic inflammation colibactin cytolethaldistending toxin DNA damage DNA damage response genomic instability tumor induction progression Correspondence T. Frisan Department of Celland Molecular Biology Karolinska Institutet Box 285 S-171 77 Stockholm Sweden Fax 46 8 337412 Tel 46 8 52486385 E-mail Received 1 March 2011 revised 4 April 2011 accepted 13 April 2011 doi 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. Introduction Epidemiological evidence has linked chronic bacterial .

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