DIETARY-FAT AND FIBER DIFFERENTIALLY ALTER INTRACELLULAR 2ND MESSENGERS DURING TUMOR-DEVELOPMENT IN RAT COLON

The effect of fat, fiber and carcinogen on colonic epithelial intracel lular second messengers 1,2-diacyl-sn-glycerol (DAG), ceramide, and th e steady-state level of phospholipase C (PLC-gamma 1) was determined i n 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 o il), two types of fiber (cellulose or pectin), two injected subgroups (with or without azoxymethane (AOM), and two time points (15 and 37 we eks). At the final time point (37 weeks) there were an additional 20 r ats per diet in each of the carcinogen-treated groups for tumor analys es only (n = 80), for a total of 240 animals in the entire study, At e ach time point (15 and 37 weeks), 80 rats were killed and colonic muco sa obtained for DAG, ceramide and PLC-gamma 1 assays, At the first tim e point (15 weeks), there was no microscopic evidence of tumors, At th e final time point (37 weeks), fish oil resulted in a lower proportion of animals with adenocarcinomas relative to corn oil feeding (56.1% v ersus 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-gamma 1 co mpared 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 anim als, Moreover, rats injected with AOM had a significantly (P < 0.02) e levated colonic mucosal DAG/ceramide ratio versus saline injected anim als, In contrast, dietary fiber had no effect on any of the parameters measured at 15 weeks, However, at 37 weeks post-injection, dietary fi ber significantly altered DAG (P < 0.02), and PLC-gamma 1 expression ( P < 0.05) in the absence of an effect on tumor incidence, These data d emonstrate that the ability of dietary fish oil to reduce experimental colon carcinogenesis may be mediated by changes in colonic intracellu lar mediators during the initial stages of tumorigenesis.