EFFECTS OF DIETARY-FAT AND A VEGETABLE-FRUIT MIXTURE ON THE DEVELOPMENT OF INTESTINAL NEOPLASIA IN THE APC(MIN) MOUSE

The variation in colorectal cancer (CRC) incidence world-wide strongly suggests a role for dietary influences. Based on epidemiological data , protective effects of vegetables and fruit intake on CRC are widely claimed, while other data indicate a possible increased CRC risk from (higher) dietary fat intake. Therefore, we have investigated single an d interactive effects of dietary fat and a vegetable-fruit mixture (VF M) in the Apc(Min) mouse, a mouse model for multiple intestinal neopla sia, In this study, four different diets (A-D) were compared, which we re either low in fat (20% energy diets A/B) or high in fat (40% energy diets CID), In addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced by a freeze-dried VFM, The diets were balanced s o that they only differed among each other in fat/carbohydrate content and the presence of specific plant-constituents. Because the initiati on of intestinal tumors in Apc(Min) mice occurs relatively early in li fe, exposure to the diets was started in utero, Without the addition o f VFM, mice maintained at a high-fat diet did not develop significantl y higher numbers of small or large intestinal adenomas than mice maint ained at a low-fat diet. VFM added to a low-fat diet significantly low ered multiplicity of small intestinal polyps (from 16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male Apc(Min) mice only . Strikingly, addition of VFM to female mice maintained on a low-fat d iet and to both sexes maintained on a high-fat diet significantly enha nced intestinal polyp multiplicity (from 16.5 to 26.7 polyps/mouse). I n conclusion, our results indicate that neither a lower fat intake nor consumption of VFM included in a high-fat diet decreases the developm ent of polyps in mice genetically predisposed to intestinal tumor deve lopment.