Effect of dietary vitamin E on the development of altered hepatic foci and hepatic tumors induced by the peroxisome proliferator ciprofibrate.
The purpose of this study was to determine the effect of the dietary antioxidant vitamin E on hepatocarcinogenesis by peroxisome proliferators which, it is hypothesized, induce tumors by increased production of hydrogen peroxide or other oxygen radicals. Rats were fed diets containing the peroxisome proliferator ciprofibrate and one of three concentrations (10, 50, or 500 ppm) of alpha-tocopheryl acetate for 6 months or 21 months. The incidence of hepatic tumors and the number and volume of gamma-glutamyl-transpeptidase-positive, ATPase-negative, glucose-6-phosphatase-negative, and glucose-6-phosphatase-positive foci were quantified. No tumors or altered hepatic foci were seen at 6 months, but at 21 months the incidence of hepatic tumors and the number and volume of altered hepatic foci were increased in rats fed higher levels of vitamin E. Indices of oxidative damage--concentrations of malonaldehyde, conjugated dienes, and lipid-soluble fluorescence products--were not affected or were lower in rats fed higher amounts of vitamin E; the enhancing effect of vitamin E on the development of altered hepatic foci and hepatic tumors, therefore, was not related to the induction of cellular oxidative damage. Hepatic peroxisomal fatty acid beta-oxidation and vitamin C concentrations were not affected by vitamin E, whereas the glutathione concentration was decreased in rats fed higher amounts of vitamin E. This study shows that increasing the vitamin E content of the diet enhances ciprofibrate-induced hepatocarcinogenesis, but the mechanism of this effect is unclear.
Glauert
H P
HP
Department of Nutrition and Food Science, Veterans Administration Hospital, Lexington, KY.
Beaty
M M
MM
Clark
T D
TD
Greenwell
W S
WS
Tatum
V
V
Chen
L C
LC
Borges
T
T
Clark
T L
TL
Srinivasan
S R
SR
Chow
C K
CK
D000251:Adenosine Triphosphatases / Q000032:analysis; D000818:Animals; D002994:Clofibrate / Q000031:analogs & derivatives*; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D004357:Drug Synergism; D005260:Female; D058607:Fibric Acids; D005952:Glucose-6-Phosphatase / Q000032:analysis; D008099:Liver / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000097:blood / Q000139:chemically induced* / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D014810:Vitamin E / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005723:gamma-Glutamyltransferase / Q000032:analysis
D058607:Fibric Acids; D014810:Vitamin E; D002995:Clofibric Acid; D005723:gamma-Glutamyltransferase; D005952:Glucose-6-Phosphatase; D000251:Adenosine Triphosphatases; C019304:ciprofibrate; D002994:Clofibrate