Stephenson, Marissa (2003) DNA damage induction by 'Helicobacter pylori'. (MSc(R) thesis), Kingston University, .

Abstract

Infection with ‘Helicobacter pylori’ has been associated with the development of gastric adenocarcinoma in humans. A number of routes have been implicated, primarily oxidative DNA damage resulting from chronic inflammation, which accompanies infection. DNA damage has however been demonstrated in human cells after ‘in vitro’ incubation with ‘H. pylori’ sonicate (Ning et al 1996, Schmausser et aI 1999). Using both the’ in vitro’ micronucleus and fragment length analysis using restriction enzymes (FLARE) assays, this study investigates the DNA damaging potential of eight clinical isolates and three type strains, (including two isogenic mutants) of ‘H. pylori’, in addition to two isolates of the related organism ‘Campylobacter jejuni’ on three cultured human cell lines. ‘H. pylori’ has been shown in this study to form a low level, non-cytolethal infection in two gastro-intestinal adenocarcinoma cell lines and a cervical carcinoma cell line. Increasing periods of incubation with all eight Cytotoxin associated gene A (CagA) toxin producing strains used, resulted in cytokinesis blocked cells exhibiting a proportional increase in micronucleation. Neither of the two CagA-ve strains tested induced this effect, nor was it dependent on the Vacuolating cytotoxin (VacA) status of the organism. The FLARE assay detected significant amounts of oxidative DNA damage in cultured gastrointestinal cells after a 72 hour incubation with 3 different clinical isolates of CagA+ve ‘H. pylori’. The results of this study have demonstrated an association between ‘H. pylori’ infection and the development of oxidative host cell DNA damage, in a process in which the CagA toxin may be intrinsically involved. As tumour induction is a known consequence of oxidative DNA damage, chronic infection with the organism may lead to development of adenocarcinoma of the stomach.

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