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Gastroenterology. 2009 Oct;137(4):1367-79.e1-6. doi: 10.1053/j.gastro.2009.07.041. Epub 2009 Jul 19.

Diet synergistically affects helicobacter pylori-induced gastric carcinogenesis in nonhuman primates.

Author information

1
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland.

Abstract

BACKGROUND & AIMS:

Gastric cancer results from a combination of Helicobacter pylori (H pylori) infection, exposure to dietary carcinogens, and predisposing genetic make-up. Because the role of these factors in gastric carcinogenesis cannot be determined readily in human beings, the present study examined the role of an oral carcinogen and H pylori infection in rhesus monkeys.

METHODS:

Gastroscopies were performed in 23 monkeys assigned to 4 groups: controls; nitrosating carcinogen ethyl-nitro-nitrosoguanidine administration alone; inoculation of a virulent H pylori strain alone (H); and ethyl-nitro-nitrosoguanidine in combination with H pylori (EH). Follow-up gastroscopies and biopsies were performed at 3-month intervals for 5 years for pathologic and molecular studies.

RESULTS:

Postinoculation, H and EH groups showed persistent infection and antral gastritis. Starting at 2 and 5 years, respectively, gastric intestinal metaplasia and intraepithelial neoplasia developed in 3 EH monkeys but in no other groups. Transcriptional analysis of biopsy specimens at 5 years revealed group-specific expression profiles, with striking changes in EH monkeys, plus a neoplasia-specific expression profile characterized by changes in multiple cancer-associated genes. Importantly, this neoplastic profile was evident in nonneoplastic mucosa, suggesting that the identified genes may represent markers preceding cancer.

CONCLUSIONS:

Gastric intraglandular neoplasia is induced in primates when H pylori infection is associated with consumption of a carcinogen similar to the nitrosamines found in pickled vegetables, suggesting that H pylori and the carcinogen synergistically induce gastric neoplasia in primates.

PMID:
19622359
PMCID:
PMC2774828
DOI:
10.1053/j.gastro.2009.07.041
[Indexed for MEDLINE]
Free PMC Article
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