Carcinogenesis, Vol 18, 755-759, Copyright © 1997 by Oxford University Press
C Ip, C Jiang, HJ Thompson and JA Scimeca
Conjugated linoleic acid (CLA) has been reported to have significant
activity in inhibiting mammary carcinogenesis. A major objective of this
study was to evaluate how changes in the concentration of CLA in mammary
tissue as a function of CLA exposure/withdrawal were correlated with 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 showed that the incorporation of CLA
was much higher in neutral lipids than 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 closely the rate of occurrence
of new tumors in the target tissue. It appears 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 determined. A secondary goal of this study was
to investigate whether CLA might selectively inhibit clonal expansion of
DMBA- initiated mammary epithelial cells with wild-type versus codon 61
mutated Ha-ras genes. Approximately 16% of carcinomas in the control group
(without CLA) were found to express codon 61 ras mutation. Although
continuous treatment with CLA reduced the total number of carcinomas by
70%, it did not alter the proportion of ras mutant versus wild-type
carcinomas, suggesting that CLA inhibits mammary carcinogenesis
irrespective of the presence or absence of the ras mutation.
ARTICLES
Retention of conjugated linoleic acid in the mammary gland is associated with tumor inhibition during the post-initiation phase of carcinogenesis
Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
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