Helicobacter hepaticus promotes azoxymethane-initiated colon tumorigenesis in BALB/c-IL10-deficient mice.
The BALB/c-IL10 null mouse strain develops colitis and colitis-associated adenocarcinomas, and is a model for idiopathic inflammatory bowel disease. We tested the hypotheses that (i) azoxymethane (AOM), a carcinogen that targets the colon, synergizes with the colonic inflammation inherent in the BALB/c-IL10 null mouse resulting in an increase in incidence, multiplicity and/or progression of AOM-induced tumors or colitis-associated adenocarcinomas; and (ii) prior infection with Helicobacter hepaticus, a common enterohepatic bacterial pathogen in many research mouse colonies, increases the incidence, multiplicity and/or progression of AOM-induced colon tumors or colitis-associated adenocarcinomas in the BALB/c-IL10 null mouse. We show that, within the timeframe examined, AOM-induced colon tumors in the BALB/c-IL10 null mouse were grossly and microscopically similar in appearance to AOM-induced colon tumors in the wild type BALB/cJ mouse. No colitis-associated adenocarcinomas were identified. Infection with H. hepaticus prior to AOM-treatment also did not result in colitis-associated adenocarcinomas but did result in a significant increase in the incidence of AOM-induced colon tumors relative to AOM treatment alone. The AOM-induced adenomas were predominantly exophytic and nodular or polypoid and localized to the distal colon. These results suggest that H. hepaticus promotes AOM-induced tumorigenesis in the BALB/c-IL10 null mouse.
Nagamine
Claude M
CM
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Rogers
Arlin B
AB
Fox
James G
JG
Schauer
David B
DB
D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology / Q000821:virology; D000818:Animals; D001397:Azoxymethane / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000821:virology; D003106:Colon / Q000187:drug effects* / Q000821:virology; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000473:pathology / Q000821:virology; D016481:Helicobacter Infections / Q000139:chemically induced / Q000473:pathology* / Q000821:virology; D044923:Helicobacter hepaticus / Q000472:pathogenicity*; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout
D002273:Carcinogens; D016753:Interleukin-10; D001397:Azoxymethane