Dietary supplementation of conjugated linoleic acid reduces colon tumor incidence in DMH-treated rats by increasing apoptosis with modulation of biomarkers

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Los Angeles County, Calif.), 2003-09, Vol.19 (9), p.772-777
• Main Authors: Kim, Kyung-Hee, Park, Hyun-Suh
• Format: Article
• Language: English
• Subjects: 1,2-diacylglycerol; 1,2-Dimethylhydrazine; Animals; apoptosis; Apoptosis - drug effects; Biomarkers; Body weight; Carcinogenesis; Carcinogens; Colon; Colonic Neoplasms - epidemiology; Colonic Neoplasms - prevention & control; conjugated linoleic acid; Diet; Dietary Supplements; Dose-Response Relationship, Drug; eicosanoid; Fatty acids; Fatty Acids, Omega-3 - administration & dosage; Fatty Acids, Omega-3 - pharmacology; Fish oils; Hogs; Incidence; Linoleic Acid - administration & dosage; Linoleic Acid - pharmacology; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Rodents; Signal Transduction; tumor incidence; Tumors
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/S0899-9007(03)00098-4

We investigated the effects of conjugated linoleic acid (CLA) on tumor incidence, apoptosis, eicosanoid formation, 1,2-diacylglycerol (DAG), and fatty acid profiles of colonic mucosa in 1,2-dimethylhydrazine–treated rats fed different types of dietary fats. One hundred twenty male 7-wk-old Sprague-Dawley rats were assigned to a beef tallow (BT) diet or a fish oil (FO) diet; each group was further divided into two groups, one with CLA supplementation (BTC and FOC) and the other without (BT and FO). All groups were fed for 30 wk on experimental diets that contained 12% (w/w) dietary fat (including 1% CLA for the BTC and FOC groups) and were intramuscularly injected with 1,2-dimethylhydrazine for 6 wk, for a total dose of 180 mg/kg of body weight. Rats fed the FOC, BTC, or FO (ω-3 fatty acids, mainly docosahexaenoic acid) showed a reduced incidence of tumors, increased apoptotic index values ( P < 0.05), and lower levels of eicosanoids (prostaglandin E 2 and thromboxane B 2) and DAG in colonic mucosa ( P < 0.05). CLA and docosahexaenoic acid were incorporated into membrane phospholipids and significantly reduced the distribution of arachidonic acid in colonic mucosal phospholipids. Because CLA and ω-3 fatty acids reduced tumor incidence and levels of cell response regulators (prostaglandin E 2, thromboxane B 2, and DAG), they may share at least one common path of action in promoting the apoptotic process of colon carcinogenesis. These results suggested that increased apoptosis by dietary CLA may be attributed, at least in part, to changes in arachidonic acid metabolism in rats. Therefore, CLA may have anticarcinogenic effects by inducing apoptosis through modification of signal transduction in colonic mucosal cells.