RETENTION OF CONJUGATED LINOLEIC-ACID IN THE MAMMARY-GLAND IS ASSOCIATED WITH TUMOR-INHIBITION DURING THE POSTINITIATION PHASE OF CARCINOGENESIS

Conjugated linoleic acid (CLA) has been reported to have significant a ctivity in inhibiting mammary carcinogenesis, A major objective of thi s study was to evaluate how changes in the concentration of CLA in mam mary tissue as a function of CLA exposure/withdrawal were correlated w ith the rate of occurrence of mammary carcinomas, Rats treated with a single dose of dimethylbenz[a]anthracene (DMBA) at 50 days of age were given 1% CLA in the diet for either 4 weeks, 8 weeks or continuously following carcinogen administration. No cancer protection was evident in the 4 or 8 week-CLA treatment groups, Significant tumor inhibition was observed only in rats that were given CLA for the entire duration of the experiment (20 weeks). Analysis of CLA in the mammary gland sho wed that the incorporation of CLA was much higher in neutral lipids th an in phospholipids. When CLA was removed from the diet, neutral lipid - and phospholipid-CLA returned to basal values in about 4 and 8 weeks , respectively, The rate of disappearance of neutral lipid-CLA (rather than phospholipid-CLA) subsequent to CLA withdrawal paralleled more c losely the rate of occurrence of new tumors in the target tissue, It a ppears that neutral lipid-CLA may be a more sensitive marker of tumor protection than phospholipid-CLA, However, the physiological relevance of CLA accumulation in mammary lipids is unclear and remains to be de termined, A secondary goal of this study was to investigate whether CL A might selectively inhibit clonal expansion of DMBA-initiated mammary epithelial cells with wildtype versus codon 61 mutated Hn-ras genes, Approximately 16% of carcinomas in the control group (without CLA) wer e found to express codon 61 ras mutation, Although continuous treatmen t with CLA reduced the total number of carcinomas by 70%, it did not a lter the proportion of ms mutant versus wild-type carcinomas, suggesti ng that CLA inhibits mammary carcinogenesis irrespective of the presen ce or absence of the ras mutation.