Dietary trans-10, cis-12 and cis-9,trans-11 conjugated linoleic acids induce apoptosis in the colonic mucosa of rats treated with 1,2-dimethylhydrazine.
We have previously shown that a diet containing a mixture of conjugated linoleic acid (CLA) isomers reduces the incidence of colon tumors in rats treated with 1,2-dimethylhydrazine (DMH). The present study examined which of the two main CLA isomers, trans-10,cis-12 CLA (t10c12) or cis-9,trans-11 CLA (c9t11), decreases colon tumor numbers and the mechanisms for this effect. Six-week-old, male Sprague-Dawley rats were intramuscularly injected with 15 mg/kg of DMH twice per week for 6 weeks and fed a control diet, 1% t10c12, or 1% c9t11 for 30 weeks. The experimental diets were initiated simultaneously with DMH injection. The tumor numbers were decreased and the apoptotic index was significantly increased in the colonic mucosa of the t10c12 and c9t11 groups, when the results were compared with those of the control group. The protein levels of Bcl-2 and cyclooxygenase-2 were significantly decreased, but Bax levels were increased in both of the CLA isomer groups. The thromboxane B(2) levels in colonic mucosa were substantially lower in the two CLA isomer groups than in the control group. However, there was no difference in these parameters between the CLA isomer groups. We have demonstrated that diets containing 1% t10c12 and c9t11 were equally effective in reducing tumor numbers and inducing apoptosis in the colonic mucosa of rats treated with DMH. These results indicate that Bcl-2 family protein levels are associated with CLA-induced apoptosis in the colonic mucosa of DMH-treated rats.
Park
Hyun Suh
HS
Department of Food and Nutrition, Kyung Hee University, Seoul, Korea.
Chun
Chang Soo
CS
Kim
Sung
S
Ha
Yeong Lae
YL
Park
Jung Han Yoon
JH
D019813:1,2-Dimethylhydrazine / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003106:Colon / Q000737:chemistry / Q000166:cytology*; D051546:Cyclooxygenase 2 / Q000032:analysis; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000737:chemistry / Q000166:cytology; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013929:Thromboxane B2 / Q000032:analysis; D051028:bcl-2-Associated X Protein / Q000032:analysis
D004042:Dietary Fats, Unsaturated; D044243:Linoleic Acids, Conjugated; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C496197:trans-10,cis-12-conjugated linoleic acid; D013929:Thromboxane B2; D051546:Cyclooxygenase 2; D019813:1,2-Dimethylhydrazine