MORPHOLOGICAL AND BIOCHEMICAL STATUS OF THE MAMMARY-GLAND AS INFLUENCED BY CONJUGATED LINOLEIC-ACID - IMPLICATION FOR A REDUCTION IN MAMMARY-CANCER RISK
H. Thompson et al., MORPHOLOGICAL AND BIOCHEMICAL STATUS OF THE MAMMARY-GLAND AS INFLUENCED BY CONJUGATED LINOLEIC-ACID - IMPLICATION FOR A REDUCTION IN MAMMARY-CANCER RISK, Cancer research, 57(22), 1997, pp. 5067-5072
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.