Helicobacter hepaticus Infection Promotes Colon Tumorigenesis in the BALB/c-Rag2⁻/⁻ ApcMin/⁺ Mouse

• Published in: Infection and Immunity Vol. 76; no. 6; pp. 2758 - 2766
• Main Authors: Nagamine, Claude M, Sohn, Jane J, Rickman, Barry H, Rogers, Arlin B, Fox, James G, Schauer, David B
• Format: Journal Article
• Language: English
• Published: American Society for Microbiology 01.06.2008; American Society for Microbiology (ASM)
• Subjects: Host Response and Inflammation
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.01604-07

Adenomatous polyposis coli (APC) mutations are linked to human and mouse colorectal cancers. The Apc multiple intestinal neoplasia (Min) mouse mutation causes adenomas to develop throughout the small and large intestines. The BALB-Min (C.B6-ApcMin/⁺) congenic strain was generated by backcrossing into BALB/c the ApcMin allele from C57BL/6J-ApcMin/⁺ mice. BALB-Min mice have a low tumor multiplicity (27.4 small intestine tumors/mouse) and a relatively long life span (>1 year) that makes them amenable to long-term studies. To investigate the interplay of the adaptive immune system and intestinal tumorigenesis, the immunodeficient compound mutant strain BALB-RagMin (C.Cg-Rag2⁻/⁻ ApcMin/⁺) was generated. BALB-RagMin mice had a significant increase in tumors in the small, but not large, intestine relative to their BALB-Min counterparts (43.0 versus 24.0 tumors/mouse, respectively). The results suggest that the adaptive immune system plays a role in either the elimination or the equilibrium phase of cancer immunoediting in the small intestine in this model. We investigated the effect of the enterohepatic bacterial pathogen Helicobacter hepaticus on liver and intestine tumorigenesis in BALB-RagMin mice. H. hepaticus-infected BALB-RagMin mice developed moderate hepatitis, moderate typhlitis, and mild colitis. There were no differences in small intestine and cecal tumor multiplicity, regionality, or size relative to that in uninfected mice. However, H. hepaticus-infected BALB-RagMin mice had a significant increase in colon tumor incidence relative to uninfected BALB-RagMin mice (23.5% versus 1.7%, respectively). The data suggest that H. hepaticus, which is present in many research colonies, promotes colon tumorigenesis in the BALB-RagMin mouse and that it has the potential to confound colon tumorigenesis studies.