Carcinogenesis, Vol. 20, No. 6, 1019-1024,
June 1999
© 1999 Oxford University Press
Molecular Epidemiology and Cancer Prevention |
Decrease in linoleic acid metabolites as a potential mechanism in cancer risk reduction by conjugated linoleic acid
Dipartimento di Biologia Sperimentale, Sezione di Patologia Sperimentale, Universita degli Studi di Cagliari, Cittadella Universitaria, 09042 Monserrato, Cagliari, Italy,
1 Division of Laboratory Research, AMC Cancer Research Center, Denver, CO 80214, USA and
2 Department of Experimental Pathology, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263, USA
Previous research suggested that conjugated linoleic acid (CLA) feeding during the period of pubescent mammary gland development in the rat resulted in diminished mammary epithelial branching which might account for the reduction in mammary cancer risk. Terminal end buds (TEB) are the primary sites for the chemical induction of mammary carcinomas in rodents. One of the objectives of the present study was to investigate the modulation of TEB density by increasing levels of dietary CLA and to determine how this might affect the risk of methylnitrosourea-induced mammary carcinogenesis. The data show a graded and parallel reduction in TEB density and mammary tumor yield produced by 0.5 and 1% CLA. No further decrease in either parameter was observed when CLA in the diet was raised to 1.5 or 2%. Thus, optimal CLA nutrition during pubescence could conceivably control the population of cancer-sensitive target sites in the mammary gland. Since both CLA and linoleic acid are likely to share the same enzyme system for chain desaturation and elongation, it is possible that increased CLA intake may interfere with the further metabolism of linoleic acid. Fatty acid analysis of total lipid showed that CLA and CLA metabolites continued to accumulate in mammary tissue in a dose-dependent manner over the range 0.5–2% CLA. There was no perturbation in tissue linoleic acid, however, linoleic acid metabolites (including 18:3, 20:3 and 20:4) were consistently depressed by up to 1% CLA. Of particular interest was the significant drop in 20:4 (arachidonic acid), which is the substrate for the cyclooxygenase and lipoxygenase pathways of eicosanoid biosynthesis. Thus the CLA dose–response effect on arachidonic acid suppression corresponded closely with the CLA dose–response effect on cancer protection in the mammary gland. This information is critical in providing new insights regarding the biochemical action of CLA.
Abbreviations: CD, conjugated diene; CLA, conjugated linoleic acid; MNU, methylnitrosourea; TEB, terminal end bud.
3 To whom correspondence should be addressed Email: cip{at}sc3101.med.buffalo.edu
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