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Mutagenic potency of Helicobacter pylori in the gastric mucosa of mice is determined by sex and duration of infection
- Publication Year :
- 2010
- Publisher :
- National Academy of Sciences, 2010.
-
Abstract
- Helicobacter pylori is a human carcinogen, but the mechanisms evoked in carcinogenesis during this chronic inflammatory disease remain incompletely characterized. We determined whether chronic H. pylori infection induced mutations in the gastric mucosa of male and female gpt delta C57BL/6 mice infected for 6 or 12 mo. Point mutations were increased in females infected for 12 mo. The mutation frequency in this group was 1.6-fold higher than in uninfected mice of both sexes ( P < 0.05). A:T-to-G:C transitions and G:C-to-T:A transversions were 3.8 and 2.0 times, respectively, more frequent in this group than in controls. Both mutations are consistent with DNA damage induced by oxidative stress. No increase in the frequency of deletions was observed. Females had more severe gastric lesions than males at 6 mo postinfection (MPI; P < 0.05), but this difference was absent at 12 MPI. In all mice, infection significantly increased expression of IFN γ, IL-17 , TNF α, and iNOS at 6 and 12 mo, as well as H. pylori –specific IgG1 levels at 12 MPI ( P < 0.05) and IgG2c levels at 6 and 12 MPI ( P < 0.01 and P < 0.001). At 12 MPI, IgG2c levels in infected females were higher than at 6 MPI ( P < 0.05) and also than those in infected males at 12 MPI ( P < 0.05). Intensity of responses was mediated by sex and duration of infection. Lower H. pylori colonization indicated a more robust host response in females than in males. Earlier onset of severe gastric lesions and proinflammatory, Th1-biased responses in female C57BL/6 mice may have promoted mutagenesis by exposing the stomach to prolonged oxidative stress.
- Subjects :
- Male
medicine.medical_specialty
Time Factors
Gene Expression
Nitric Oxide Synthase Type II
Mice, Transgenic
medicine.disease_cause
Proinflammatory cytokine
Helicobacter Infections
Mice
Internal medicine
Gastric mucosa
medicine
Animals
Humans
Pentosyltransferases
Mutation frequency
Sex Characteristics
Multidisciplinary
biology
Helicobacter pylori
Stomach
Escherichia coli Proteins
Biological Sciences
biology.organism_classification
Antibodies, Bacterial
Mice, Inbred C57BL
Oxidative Stress
medicine.anatomical_structure
Endocrinology
Gastric Mucosa
Mutagenesis
Gastritis
Immunoglobulin G
Immunology
Mutation
Cytokines
Female
medicine.symptom
Carcinogenesis
Oxidative stress
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....9c091c57d17310710dfd1d796652b922