Effects of dietary fat and a vegetable-fruit mixture on the development of intestinal neoplasia in the ApcMin mouse

The variation in colorectal cancer (CRC) incidence worldwide stronglysuggests a role for dietary influences. Based on epidemiological data,protective effects of vegetables and fruit intake on CRC are widelyclaimed, while other data indicate a possible increased CRC risk from(higher) dietary fat intake. Therefore, we have investigated single andinteractive effects of dietary fat and a vegetable-fruit mixture (VFM) inthe ApcMin mouse, a mouse model for multiple intestinal neoplasia. In thisstudy, four different diets (A-D) were compared, which were either low infat (20% energy diets A/B) or high in fat (40% energy diets C/D). Inaddition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replacedby a freeze-dried VFM. The diets were balanced so that they only differedamong each other in fat/carbohydrate content and the presence of specificplant-constituents. Because the initiation of intestinal tumors in ApcMinmice occurs relatively early in life, exposure to the diets was started inutero. Without the addition of VFM, mice maintained at a high-fat diet didnot develop significantly higher numbers of small or large intestinaladenomas than mice maintained at a low-fat diet. VFM added to a low-fatdiet significantly lowered multiplicity of small intestinal polyps (from16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in maleApcMin mice only. Strikingly, addition of VFM to female mice maintained ona low-fat diet and to both sexes maintained on a high-fat dietsignificantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7polyps/mouse). In conclusion, our results indicate that neither a lower fatintake nor consumption of VFM included in a high-fat diet decreases thedevelopment of polyps in mice genetically predisposed to intestinal tumordevelopment.