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Helicobacter pylori is not mutagenic in Ames test
Department of Surgery, Örebro Medical Centre Hospital, Örebro, Sweden.
Department of Surgery, Örebro Medical Centre Hospital, Örebro, Sweden.
2001 (English)In: Cancer Research, Therapy and Control, ISSN 1064-0525, Vol. 11, no 2, 167-173 p.Article in journal (Refereed) Published
Abstract [en]

Problem: Helicobacter pylori is classified as a class 1 carcinogen. However, the role of Helicobacter pylori in the initiation and promotion of gastric cancer is not known.

Methods: Mutagenicity has been measured in pure cultures of the cytotoxic Helicobacter pylori strains Ca 18 and NCTC 11637 and in extracts of Helicobacter pylori infected mouse stomach mucosa using the Salmonella mutagenicity test (Ames test). Chemiluminiscence assay was also used to verify the bacterial effect on inflammatory leukocytes.

Results: All Helicobacter strains studied induced a strong oxidative burst of polymorphonuclear leukocytes (PMNL). No direct or indirect mutagenic activity was found.

Conclusions: This confirm the concept that Helicobacter pylori is neither genotoxic per se nor indirectly by inducing mutagenic activity in gastric mucosa. Other mechanisms seems to play a role in the complex, multistep, and multifactorial process of gastric carcinogenesis.

Place, publisher, year, edition, pages
2001. Vol. 11, no 2, 167-173 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-81127OAI: oai:DiVA.org:liu-81127DiVA: diva2:550682
Available from: 2012-09-07 Created: 2012-09-07 Last updated: 2012-09-07Bibliographically approved
In thesis
1. Helicobacter pylori and gastric carcinogenesis: An experimental study of some preneoplastic events
Open this publication in new window or tab >>Helicobacter pylori and gastric carcinogenesis: An experimental study of some preneoplastic events
2001 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Half the population in the world is chronically infected with H.pylori. This infection has been proven to be associated with gastritis, duodenal and gastric ulcers but also with gastric cancer and MALT-lymphoma. The aims of this thesis were to explore some possible mechanisms by which H.pylori may contribute to the onset of gastric cancer.

The first approach was to study whether H. pylori is mutagenic. Three different H.pylori strains (NCTC 11637, Ca 18, 13/12), all cagA and VacApositive, were studied with the Salmonella mutagenicity assay (the Ames test). No dose-response curve and no increase in revertants were seen. These results show that H. pylori is not likely to be mutagenic.

A special feature ofH.pylori gastritis is that it is practically always linked to inflammation with varying degrees of mucosal activity. Neutrophils and monocytes produce and liberate nitric oxide and oxygen radicals, which are capable of inducing mutations of DNA. In order to test if the bacterium alone or together with bile could affect lenkocytes to produce mutagenic substances, some in vitro experiments were performed. The Ames test was used on neutrophils from blood donors. The neutrophils· were exposed to H. pylori and/or bile. A time-dependent response was found, where neutrophils exposed for two hours or more showed significant mutagenic activity in 5 of 19 experiments. The combination with bile gave the highest response. In a follow up of these findings, no mutagenic activity was found in H. pylori-infected mouse mucosa when tested for mutagenic substances with the Ames test.

A second approach was to develop in vivo models of H. pylori gastritis by inoculating Wistar rats and C57BL/6 mice with species-adapted H. pylori strains. An increased cell proliferation was seen in infected animals whereas, the apoptotic rate was unaffected compared with non-infected controls. This different cell response may favour gastric carcinogenesis. Furthermore, H.pylori significantly promoted cell proliferation in rats exposed to bile, and in mice given the combination of MNNG and bile.

A third approach was to study the immunohistochemistry for the expression of the enzyme COX-2 and the protein Bcl-2 in rats receiving different combinations ofH.pylori, MNNG and bile. H.pylori enhanced Bcl-2 expression in antrum mucosa and also increased the COX-2 expression in corpus mucosa. The COX-2 expression correlated with increased cell proliferation in antrum but not with apoptosis. This change in COX-2 and Bcl-2 may also promote the development of neoplasia.

In conclusion, H. pylori may promote gastric carcinogenesis in several ways. Thus neutrophils that are accumulated in H.pylori-infected mucosa, may give rise to mutagenic substances. Moreover, H.pylori infection is associated with increased cell proliferation and unchanged apoptosis, which increases the risk for mitotic errors and mutations from endo- and exogenous carcinogens. The increased cell proliferation may be induced by a simultaneously increased COX -2 expression. The enhanced Bcl-2 expression in antrum that was corrolated to increased cell proliferation, also favours tumour development.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2001. 88 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 681
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25683 (URN)10059 (Local ID)91-7219-968-7 (ISBN)10059 (Archive number)10059 (OAI)
Public defence
2001-06-01, Wilandersalen, Regionsjukhuset, Örebro, 10:00 (Swedish)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-09-07Bibliographically approved

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