Helicobacter pylori impairs DNA mismatch repair in gastric epithelial cells

Kim, Jae J.; Hong, Tao; Carloni, Emilia; Leung, Wai K.; Graham, David Y.; Sepulveda, Antonia R.

doi:10.1053/gast.2002.34751

Cited by 142 publications

(120 citation statements)

References 42 publications

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“…Previous reports using cells infected at high MOI have suggested that H. pylori affect MMR gene expression and cause increased cell death as well as growth inhibition (8,10). Expression of MMR proteins are affected by cell growth (29) and bacterial-induced growth inhibition could lead to decreased MMR expression.…”

Section: Resultsmentioning

confidence: 99%

Helicobacter pylori Infection Induces Genetic Instability of Nuclear and Mitochondrial DNA in Gastric Cells

Machado

Figueiredo

Touati

et al. 2009

Clinical Cancer Research

125

102

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Purpose: Helicobacter pylori is a major cause of gastric carcinoma. To investigate a possible link between bacterial infection and genetic instability of the host genome, we examined the effect of H. pylori infection on known cellular repair pathways in vitro and in vivo. Moreover, various types of genetic instabilities in the nuclear and mitochondrial DNA (mtDNA) were examined. Experimental Design: We observed the effects of H. pylori infection on a gastric cell line (AGS), on C57BL/6 mice, and on individuals with chronic gastritis. In AGS cells, the effect of H. pylori infection on base excision repair and mismatch repair (MMR) was analyzed by reverse transcription-PCR, Western blot, and activity assays. In mice, MMR expression was analyzed by reverse transcription-PCR and the CA repeat instabilities were examined by Mutation Detection Enhancement gel electrophoresis. Mutation spectra in AGS cells and chronic gastritis tissue were determined by PCR, single-stranded conformation polymorphism, and sequencing. H. pylori vacA and cagA genotyping was determined by multiplex PCR and reverse hybridization. Results: Following H. pylori infection, the activity and expression of base excision repair and MMR are down-regulated both in vitro and in vivo. Moreover, H. pylori induces genomic instability in nuclear CA repeats in mice and in mtDNA of AGS cells and chronic gastritis tissue, and this effect in mtDNA is associated with bacterial virulence. Conclusions: Our results suggest that H. pylori impairs central DNA repair mechanisms, inducing a transient mutator phenotype, rendering gastric epithelial cells vulnerable to the accumulation of genetic instability and thus contributing to gastric carcinogenesis in infected individuals.

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Section: Resultsmentioning

confidence: 99%

Helicobacter pylori Infection Induces Genetic Instability of Nuclear and Mitochondrial DNA in Gastric Cells

Machado

Figueiredo

Touati

et al. 2009

Clinical Cancer Research

125

102

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“…A few studies have shown that H. pylori cause impaired dna mismatch repair in gastric epithelial cells. Infection with H. pylori occurs more frequently in individuals with msi-positive than with msi-negative gastric cancers 39 . Compared with stable or low-level msi tumours, high-level msi tumours are associated with a better os rate in gastric cancer patients after curative surgery 40,41 .…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori Infection Predicts Favorable Outcome in Patients with Gastric Cancer

et al. 2013

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“…Ultimately, carcinogenesis requires DNA damage, which can be induced directly by H. pylori products or indirectly through oxygen free radicals released by neutrophils (118,121,122). Gastric ascorbic acid, which neutralizes free radicals, is reduced in H. pylori-positive stomachs (S112), and H. pylori can also directly interfere with the epithelial mismatch-repair system (122).…”

Section: Figurementioning

confidence: 99%

Helicobacter pylori persistence: biology and disease

Blaser¹,

Atherton²

2004

J. Clin. Invest.

773

540

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Helicobacter pylori are bacteria that have coevolved with humans to be transmitted from person to person and to persistently colonize the stomach. Their population structure is a model for the ecology of the indigenous microbiota. A well-choreographed equilibrium between bacterial effectors and host responses permits microbial persistence and health of the host but confers risk of serious diseases, including peptic ulceration and gastric neoplasia.

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Helicobacter pylori impairs DNA mismatch repair in gastric epithelial cells

Cited by 142 publications

References 42 publications

Helicobacter pylori Infection Induces Genetic Instability of Nuclear and Mitochondrial DNA in Gastric Cells

Helicobacter pylori Infection Induces Genetic Instability of Nuclear and Mitochondrial DNA in Gastric Cells

Helicobacter pylori Infection Predicts Favorable Outcome in Patients with Gastric Cancer

Helicobacter pylori persistence: biology and disease

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