Mouse models for the study of colon carcinogenesis

The study of experimental colon carcinogenesis in rodents hasa long history, dating back almost 80 years. There are manyadvantages to studying the pathogenesis of carcinogen-inducedcolon cancer in mouse models, including rapid and reproducibletumor induction and the recapitulation of the adenoma–carcinomasequence that occurs in humans. The availability of recombinantinbred mouse panels and the existence of transgenic, knock-outand knock-in genetic models further increase the value of thesestudies. In this review, we discuss the general mechanisms oftumor initiation elicited by commonly used chemical carcinogensand how genetic background influences the extent of disease.We will also describe the general features of lesions formedin response to carcinogen treatment, including the underlyingmolecular aberrations and how these changes may relate to thepathogenesis of human colorectal cancer. Abbreviations: AA, arachidonic acid; ACF, aberrant crypt foci; AOM, azoxymethane; Apc, adenomatous polyposis coli; BCAC, β-catenin-accumulated crypt; COX-2, cyclooxygenease-2; cPLA₂, cytosolic phospholipase A₂; CRC, colorectal cancer; DFMO, difluoromethylornithine; DMAB, 3,2'-dimethyl-4-aminobiphenyl; DMH, 1,2-dimethylhydrazine; DSS, dextran sodium sulfate; HCA, heterocyclic amine; IBD, inflammatory bowel disease; i.p., intraperitoneal; IQ, 2-amino-33-methylimidazo4,5-f]quinoline; MAM, methylazoxymethanol; miRNA, microRNA; MNNG, N-methyl-N'-nitro-N-nitrosoguanidine; MNU, methylnitrosourea; ODC, ornithine decarboxylase; PGDH, 15-hydroxyprostaglandin dehydrogenase; PGE₂, prostaglandin E2; PhIP, 2-amino-1-methyl-6-phenylimidazo4,5-b]pyridine; s.c., subcutaneous; TGF, transforming growth factor; TNF, tumor necrosis factor Received August 13, 2008; revised October 31, 2008; accepted November 20, 2008.