THE EFFICACY OF CONJUGATED LINOLEIC-ACID IN MAMMARY-CANCER PREVENTIONIS INDEPENDENT OF THE LEVEL OR TYPE OF FAT IN THE DIET

The objective of the present study was to investigate whether the anti carcinogenic activity of conjugated linoleic acid (CLA) is affected by the amount and composition of dietary fat consumed by the host, Becau se the anticancer agent of interest is a fatty acid, this approach may provide some insight into its mechanism of action, depending on the o utcome of these fat feeding experiments, For the fat level experiment, a custom formulated fat blend was used that simulates the fatty acid composition of the US diet, This fat blend was present at 10, 13.3, 16 .7 or 20% by weight in the diet. For the fat type experiment, a 20% (w /w) fat diet containing either corn oil (exclusively) or lard (predomi nantly) was used, Mammary cancer prevention by CLA was evaluated using the rat dimethylbenz[a]anthracene model, The results indicated that t he magnitude of tumor inhibition by 1% CLA was not influenced by the l evel or type of fat in the diet, It should be noted that these fat die ts varied markedly in their content of linoleate. Fatty acid analysis showed that CLA was incorporated predominantly in mammary tissue neutr al lipids, while the increase in CLA in mammary tissue phospholipids w as minimal, Furthermore, there was no evidence that CLA supplementatio n perturbed the distribution of linoleate or other fatty acids in the phospholipid fraction, Collectively these carcinogenesis and biochemic al data suggest that the cancer preventive activity of CLA is unlikely to be mediated by interference with the metabolic cascade involved in converting linoleic acid to eicosanoids. The hypothesis that CLA migh t act as an antioxidant was also examined, Treatment with CLA resulted in lower levels of mammary tissue malondialdehyde (an end product of lipid peroxidation), but failed to change the levels of 8-hydroxydeoxy guanosine (a marker of oxidatively damaged DNA), Thus while CLA may ha ve some antioxidant function in vivo in suppressing lipid peroxidation , its anticarcinogenic activity cannot be accounted for by protecting the target cell DNA against oxidative damage, The finding that the inh ibitory effect of CLA maximized at 1% (regardless of the availability of linoleate in the diet) could conceivably point to a limiting step i n the capacity to metabolize CLA to some active product(s) which is es sential for cancer prevention.