Decrease in linoleic acid metabolites as a potential mechanism in cancer risk reduction by conjugated linoleic acid

Previous research suggested that conjugated linoleic acid (CLA) feeding dur ing the period of pubescent mammary gland development in the rat resulted i n diminished mammary epithelial branching which might account for the reduc tion in mammary cancer risk. Terminal end buds (TEB) are the primary sites for the chemical induction of mammary carcinomas in rodents. One of the obj ectives of the present study was to investigate the modulation of TEE densi ty by increasing levels of dietary CLA and to determine how this might affe ct the risk of methylnitrosourea-induced mammary carcinogenesis. The data s how a graded and parallel reduction in TEE density and mammary tumor yield produced by 0.5 and 1% CLA. No further decrease in either parameter was obs erved when CLA in the diet was raised to 1.5 or 2%. Thus, optimal CLA nutri tion during pubescence could conceivably control the population of cancer-s ensitive target sites in the mammary gland. Since both CLA and linoleic aci d are likely to share the same enzyme system for chain desaturation and elo ngation, it is possible that increased CLA intake may interfere with the fu rther metabolism of linoleic acid. Fatty acid analysis of total lipid showe d that CEA and CLA metabolites continued to accumulate in mammary tissue in a dose-dependent manner over the range 0.5-2% CLA. There was no perturbati on in tissue linoleic acid, however, linoleic acid metabolites (including 1 8:3, 20:3 and 20:4) were consistently depressed by up to 1% CLA, Of particu lar interest was the significant drop in 20:3 (arachidonic acid), which is the substrate for the cyclooxygenase and lipoxygenase pathways of eicosanoi d biosynthesis, Thus the CLA dose-response effect on arachidonic acid suppr ession corresponded closely with the CLA dose-response effect on cancer pro tection in the mammary gland. This information is critical in providing new insights regarding the biochemical action of CLA.