Diet synergistically affects helicobacter pylori-induced gastric carcinogenesis in nonhuman primates.
OBJECTIVE
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.
Liu
Hui
H
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
Merrell
D Scott
DS
Semino-Mora
Cristina
C
Goldman
Matthew
M
Rahman
Arifur
A
Mog
Steven
S
Dubois
Andre
A
D000818:Animals; D001706:Biopsy; D002273:Carcinogens / Q000633:toxicity*; D002278:Carcinoma in Situ / Q000139:chemically induced / Q000235:genetics / Q000382:microbiology; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics; D016000:Cluster Analysis; D004260:DNA Repair; D004032:Diet / Q000009:adverse effects*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005756:Gastritis / Q000139:chemically induced / Q000235:genetics / Q000382:microbiology; D005773:Gastroscopy; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D016481:Helicobacter Infections / Q000150:complications / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D008253:Macaca mulatta; D008297:Male; D008679:Metaplasia; D008769:Methylnitronitrosoguanidine / Q000031:analogs & derivatives* / Q000633:toxicity; D020411:Oligonucleotide Array Sequence Analysis; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D013997:Time Factors
D002273:Carcinogens; D008769:Methylnitronitrosoguanidine; C013525:ENNG