Vitamin A prevents high fat diet-induced ACF development and modifies the pattern of expression of peroxisome proliferator and retinoic acid receptor m-RNA.
Some dietary compounds, among them fats, are modulators of colon cancer risk. This study reports the modulating effects of n-6, with or without vitamin A, on promotion of colon preneoplasic lesions induced by 1,2-dimethylhydrazine (DMH) and on the expression of nuclear receptors (PPARgamma, RXRalpha, and RARbeta). One group of male Fisher rats was fed a basic diet (5% safflower oil) and two groups were fed a high-fat diet (HFD, 25% safflower oil). Of these, one was supplemented with 200 IU vitamin A for 5 mo. The safflower oil contained polyunsaturated fatty acids, mainly linoleic acid (73%). The data showed an increasing effect of safflower oil-enriched diet on aberrant crypt foci occurrence and multiplicity. This effect was impaired by vitamin A supplementation. In addition, an HFD-related up-regulation of PPARgamma and a concomitant down-regulation of RARbeta mRNA expression were observed with or without chemical initiation and were prevented by vitamin A. Moreover, when treated with DMH, HFD rats exhibited a dramatically decreased expression of RXRalpha mRNA (-49%). It was hypothesized that HFD, leading to hyperexpression of PPARgamma, would produce an alteration of retinoic acid signaling and, in this way, create a background modulating colon cancer risk.
Delage
Barbara
B
Laboratory of Nutrition and Cellular Signalling, University Bordeaux 1, Talence Cedex, France.
Groubet
Rachel
R
Pallet
Véronique
V
Bairras
Céline
C
Higueret
Paul
P
Cassand
Pierrette
P
D019813:1,2-Dimethylhydrazine; D000818:Animals; D003106:Colon / Q000378:metabolism; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D004041:Dietary Fats / Q000008:administration & dosage* / Q000009:adverse effects; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D020025:Peroxisome Proliferators / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012450:Safflower Oil / Q000008:administration & dosage / Q000737:chemistry; D014801:Vitamin A / Q000378:metabolism*
D004041:Dietary Fats; D043371:Fatty Acids, Omega-6; D020025:Peroxisome Proliferators; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D014801:Vitamin A; D012450:Safflower Oil; D019813:1,2-Dimethylhydrazine