Dietary fat and fiber differentially alter intracellular second messengers during tumor development in rat colon.
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.
Jiang
Y H
YH
Faculty of Nutrition, Molecular and Cell Biology Group, Texas A&M University, College Station, 77843-2471, USA.
Lupton
J R
JR
Chang
W C
WC
Jolly
C A
CA
Aukema
H M
HM
Chapkin
R S
RS
D000230:Adenocarcinoma / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D001397:Azoxymethane; D002273:Carcinogens; D002518:Ceramides / Q000378:metabolism / Q000502:physiology; D003043:Cocarcinogenesis; D003106:Colon / Q000187:drug effects* / Q000378:metabolism* / Q000528:radiation effects; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology*; D004043:Dietary Fiber / Q000494:pharmacology*; D004075:Diglycerides / Q000378:metabolism / Q000502:physiology; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology; D051966:Phospholipase C gamma; D051381:Rats; D017207:Rats, Sprague-Dawley; D015290:Second Messenger Systems / Q000187:drug effects* / Q000528:radiation effects*; D010738:Type C Phospholipases / Q000378:metabolism / Q000502:physiology
D002273:Carcinogens; D002518:Ceramides; D004041:Dietary Fats; D004043:Dietary Fiber; D004075:Diglycerides; D007527:Isoenzymes; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D001397:Azoxymethane