Conjugated linoleic acid isomers and mammary cancer prevention.
There is increasing evidence that individual isomers of conjugated linoleic acid (CLA) may have unique biological or biochemical effects. A primary objective of this study was to determine whether there might be differences in the anticancer activity of 9,11-CLA and 10,12-CLA. This was achieved by evaluating the reduction in premalignant lesions and carcinomas in the mammary gland of rats that had been treated with a single dose of methylnitrosourea and given 0.5% of either highly purified CLA isomer in the diet. Our results showed that the anticancer efficacies of the two isomers were very similar. At 6 wk after carcinogen administration, the total number of premalignant lesions was reduced by 33-36%. At 24 wk, the total number of mammary carcinomas was reduced by 35-40%. The concentration of each CLA isomer and its respective metabolites was analyzed in the mammary fat pad. Tissue level of 10,12-CLA was much lower than that of 9,11-CLA. The pool of metabolites from each isomer was very similar between the two groups and represented only a small fraction of total conjugated diene fatty acids. Feeding of 9,11-CLA resulted in minimal changes in other unsaturated fatty acids. In contrast, feeding of 10,12-CLA produced a wider spectrum of perturbations. Small but significant increases in 16:1 and 16:2 were detected; these were accompanied by decreases in 20:2, 20:3, 20:4, 22:4, and 22:6. The above observation suggests that 10,12-CLA might be more potent than 9,11-CLA in interfering with elongation and desaturation of linoleic and linolenic acids. In summary, our study showed that, at the 0.5% dose level, the anticancer activity of 9,11-CLA and 10,12-CLA was very similar, even though accumulation of 10,12-CLA in the mammary tissue was considerably less than that of 9,11-CLA. These confounding changes of the other unsaturated fatty acids in contributing to the effect of 10,12-CLA need to be clarified.
Ip
Clement
C
Department of Experimental Pathology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. Clement.Ip@roswellpark.org
Dong
Yan
Y
Ip
Margot M
MM
Banni
Sebastiano
S
Carta
Gianfranca
G
Angioni
Elisabetta
E
Murru
Elisabetta
E
Spada
Simona
S
Melis
Maria Paola
MP
Saebo
Asgeir
A
D000818:Animals; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000139:chemically induced / Q000517:prevention & control*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005260:Female; D008041:Linoleic Acids / Q000008:administration & dosage*; D044243:Linoleic Acids, Conjugated; D008321:Mammary Glands, Animal / Q000473:pathology*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D008770:Methylnitrosourea / Q000008:administration & dosage; D011230:Precancerous Conditions / Q000139:chemically induced / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
C094849:10,12-octadecadienoic acid; D005231:Fatty Acids, Unsaturated; D008041:Linoleic Acids; D044243:Linoleic Acids, Conjugated; C046938:9,11-linoleic acid; D008770:Methylnitrosourea