MORPHOLOGICAL AND BIOCHEMICAL STATUS OF THE MAMMARY-GLAND AS INFLUENCED BY CONJUGATED LINOLEIC-ACID - IMPLICATION FOR A REDUCTION IN MAMMARY-CANCER RISK

Previous research showed that treatment with conjugated linoleic acid (CLA) during the period of active mammary gland morphogenesis was suff icient to confer a lasting protection against subsequent mammary tumor igenesis induced by methylnitrosourea, The present study was designed to characterize certain morphological and biochemical changes of the m ammary gland that might potentially render it less susceptible to canc er induction, Female Sprague Dawley rats were fed a 1% CLA diet from w eaning until about 50 days of age, The mammary gland parameters under investigation included (a) the deposition of neutral lipid, (b) the id entification and quantification of CLA and its metabolites, (c) the de nsity of the epithelium, and (d) the proliferative activity of various structural components, Our results showed that CLA treatment did not affect total fat deposition in the mammary tissue nor the extent of ep ithelial invasion into the surrounding fat pad but was able to cause a 20% reduction in the density of the ductal-lobular tree as determined by digitized image analysis of the whole mounts, This was accompanied by a suppression of bromodeoxyuridine labeling in the terminal end bu ds and lobuloalveolar buds, The recovery of desaturation and elongatio n products of CLA in the mammary gland confirmed our prior suggestion that the metabolism of CLA might be critical to risk modulation, The s ignificance of the above findings was investigated in a mammary carcin ogenesis bioassay with the use of the dimethylbenz[a]anthracene model. When CLA was started at weaning and continued for 6 months until the end of the experiment, this schedule of supplementation produced essen tially the same magnitude of mammary tumor inhibition in the dimethylb enz[a]anthracene model as that produced by 1 month of CLA feeding from weaning, The observation is consistent with the hypothesis that expos ure to CLA during the time of mammary gland maturation may modify the developmental potential of a subset of target cells that are normally susceptible to carcinogen-induced transformation.