The effect of fat, fiber and
carcinogen on colonic epithelial intracellular second messengers 1,2-diacyl-sn-glycerol (DAG),
ceramide, and the steady-state level of
phospholipase C (PLC-gamma1) was determined in 160 male Sprague-Dawley rats (10 rats per group). The study was a 2 x 2 x 2 x 2 factorial design with two types of fat (
corn oil or
fish oil), two types of fiber (
cellulose or
pectin), two injected subgroups (with or without
azoxymethane (AOM), and two time points (15 and 37 weeks). At the final time point (37 weeks) there were an additional 20 rats per diet in each of the
carcinogen-treated groups for
tumor analyses only (n = 80), for a total of 240 animals in the entire study. At each time point (15 and 37 weeks), 80 rats were killed and colonic mucosa obtained for DAG,
ceramide and
PLC-gamma1 assays. At the first time point (15 weeks), there was no microscopic evidence of
tumors. At the final time point (37 weeks),
fish oil resulted in a lower proportion of animals with
adenocarcinomas relative to
corn oil feeding (56.1 % versus 69.6 %, P < 0.05). There was no significant main effect of fiber on the percentage of animals with
tumors. At 15 weeks post-injection, AOM injected animals fed
corn oil-containing diets had a significantly (P < 0.001) higher DAG mass and steady-state levels of
PLC-gamma1 compared with AOM-injected animals fed
fish oil and saline injected rats on all diets. Animals fed
corn oil diets also had a significantly (P < 0.01) elevated mucosal
ceramide mass compared with
fish oil fed animals. Moreover, rats injected with AOM had a significantly (P < 0.02) elevated colonic mucosal DAG/
ceramide ratio versus saline injected animals. In contrast,
dietary fiber had no effect on any of the parameters measured at 15 weeks. However, at 37 weeks post-injection,
dietary fiber significantly altered DAG (P < 0.02), and
PLC-gamma1 expression (P < 0.05) in the absence of an effect on
tumor incidence. These data demonstrate that the ability of dietary
fish oil to reduce experimental colon
carcinogenesis may be mediated by changes in colonic intracellular mediators during the initial stages of
tumorigenesis.