Vaccenic acid feeding increases tissue levels of conjugated linoleic acid and suppresses development of premalignant lesions in rat mammary gland.
The objective of this report was to determine whether vaccenic acid (t11-18:1) is converted efficiently to conjugated linoleic acid (c9,t11-18:2, CLA) in rats via the delta 9-desaturase reaction and, if so, whether vaccenic acid could substitute for CLA as an anticancer agent. In Study 1, rats were fed 1%, 2%, or 3% vaccenic acid in their diet, and tissue levels of CLA and CLA metabolites were determined in liver and mammary gland. In general, concentrations of CLA and CLA metabolites increased proportionately with an increase in vaccenic acid intake, at least up to the 2% dose level. Beyond this dose, there was clearly a plateauing effect. Thus vaccenic acid concentration increased from an undetectable level in the control to 78.5 nmol/mg lipid in the liver of rats fed a 2% vaccenic acid diet. This was accompanied by an increase in CLA from 2.3 to 33.6 nmol/mg lipid. These changes were also mirrored in the mammary gland, where increases in vaccenic acid (from 27.5 to 163.2 nmol/mg lipid) and CLA (from 17.8 to 108.9 nmol/mg lipid) were similarly observed. Vaccenic acid at 2% produced a CLA concentration in the mammary gland that was historically associated with a positive response in tumor inhibition based on our past experience. This provided the basis for selecting 2% vaccenic acid in Study 2, which was designed to evaluate its efficacy in blocking the development of premalignant lesions in the rat mammary gland. In this experiment, formation of histologically identifiable pathology due to intraductal proliferation of terminal end bud cells of mammary epithelium was used as the end point of analysis at 6 wk after carcinogen administration. Treatment with vaccenic acid reduced the total number of these premalignant lesions by approximately 50%. We hypothesize that the anticancer response to vaccenic acid is likely to be mediated by its endogenous conversion to CLA via delta 9-desaturase.
Banni
S
S
Dipartimento di Biologia Sperimentale, Sezione di Patologia Sperimentale, Universita degli Studi di Cagliari, Cittadella Universitaria, 09042 Monserrato, Cagliari, Italy.
Angioni
E
E
Murru
E
E
Carta
G
G
Melis
M P
MP
Bauman
D
D
Dong
Y
Y
Ip
C
C
D015126:8,11,14-Eicosatrienoic Acid / Q000032:analysis; D000818:Animals; D016718:Arachidonic Acid / Q000032:analysis; D004032:Diet; D004848:Epithelium / Q000473:pathology; D005260:Female; D019787:Linoleic Acid / Q000032:analysis*; D008099:Liver / Q000737:chemistry; D008321:Mammary Glands, Animal / Q000737:chemistry / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000737:chemistry / Q000473:pathology / Q000517:prevention & control*; D009829:Oleic Acids / Q000008:administration & dosage* / Q000032:analysis; D011230:Precancerous Conditions / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D017965:gamma-Linolenic Acid / Q000032:analysis
D009829:Oleic Acids; D016718:Arachidonic Acid; D017965:gamma-Linolenic Acid; D019787:Linoleic Acid; D015126:8,11,14-Eicosatrienoic Acid; C050413:11-octadecenoic acid