Dietary conjugated linoleic acid (CLA) induces apoptosis of colonic mucosa in 1,2-dimethylhydrazine-treated rats: a possible mechanism of the anticarcinogenic effect by CLA.
One of the objectives of the present study was to investigate whether 1 % conjugated linoleic acid (CLA) in the diet reduced tumour incidence in the colon of 1,2-dimethylhydrazine (DMH)-treated rats. Colon cancer was induced by injecting 6-week-old, male, Sprague-Dawley rats with 15 mg/kg DMH twice per week for 6 weeks. They were fed either 1 % CLA or a control diet ad libitum for 30 weeks. Dietary CLA significantly decreased colon tumour incidence (P<0.05). Our second objective was to investigate whether apoptosis in the colon mucosa of DMH-treated rats was affected by the amount of dietary CLA and whether the changes in apoptosis were related to those in fatty acid-responsive biomarkers. For this purpose, rats were killed after being fed a diet containing 0 %, 0.5 %, 1 % or 1.5 % CLA for 14 weeks. CLA was undetected in the mucosa of rats fed the 0 % CLA diet and increased to 5.9 mg/g phospholipid in rats fed the 0.5 % diet. The apoptotic index estimated by the terminal deoxynucleotidyl transferase-mediated dUTP nick and labelling technique was increased by 251 % and the 1,2-diacylglycerol content was decreased by 57 % in rats fed 0.5 % CLA. No further changes in these variables were observed when CLA in the diet was raised to 1.0 % or 1.5 %. However, dietary CLA decreased mucosal levels of prostaglandin E2, thromboxane B2 and arachidonic acid in a dose-dependent manner. The present data indicate that dietary CLA can inhibit DMH-induced colon carcinogenesis by mechanisms probably involving increased apoptosis.
Park
H S
HS
Department of Food and Nutrition, Kyung Hee University, Seoul, Korea.
Ryu
J H
JH
Ha
Y L
YL
Park
J H
JH
D019813:1,2-Dimethylhydrazine; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015415:Biomarkers; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000178:diet therapy / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D008041:Linoleic Acids / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D002273:Carcinogens; D008041:Linoleic Acids; D019813:1,2-Dimethylhydrazine