Cancer Epidemiol Biomarkers Prev. 2003;12 (5):391-400. Point: From animal models to prevention of colon cancer. Systematic review of chemoprevention in min mice and choice of the model system

The Min (Apc(+/-)) mouse model and the azoxymethane (AOM)-rat model are the main animal models used to study the effect of dietary agents on colorectal cancer. We recently reviewed the potency of chemopreventive agents in the AOM-rat model (Corpet and Taché, 2002). Here we add the results of a systematic review of the effect of diet and agents on the tumor yield in Min mice, based on the results of 179 studies, from 71 articles, and displayed also at the website http://www.inra.fr/reseaunacre/corpet. The efficacy of agents in the Min mouse model and the AOM-rat model correlated (r=0.66, p<0.001), although some agents that afford strong inhibition in the AOM-rat and the Min mouse increase the tumor yield in the large bowel of mutant mice for reasons not yet understood. Thus, piroxicam, sulindac, celecoxib, difluoromethylornithine, and polyethylene glycol could promote carcinogenesis in the colon of mice. We also compare the results of rodent studies with those from clinical intervention studies of polyp recurrence. We found that the effect of most of the agents tested is consistent across the animal models, except the above-mentioned puzzling mouse colon. Thus our point is that the rodent models can provide guidance in the selection of prevention approaches to colon cancer, in particular suggesting the likely importance of polyethylene glycol, hesperidin, protease inhibitor, sphingomyelin, physical exercise, epidermal growth factor receptor kinase inhibitor, (+)catechin, resveratrol, fish oil, curcumin, caffeate and thiosulfonate as preventive agents. The abbreviations used are: NSAID, nonsteroidal anti-inflammatory drug; AOM, azoxymethane; Apc, adenomatous polyposis coli; PhIP, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine; PEG, polyethylene glycol; DFMO, difluoromethylornithine; COX, cyclooxygenase; PPAR, peroxisome proliferator-activated receptor; PLA-2, phospholipase A-2. ha l-0 04 11 76 8, v er si on 1 28 A ug 2 00 9