No evidence for an inhibitory effect of beta-carotene or of canthaxanthin on the initiation of liver preneoplastic foci by diethylnitrosamine in the rat.
To test whether beta-carotene or canthaxanthin can modulate the initiation of liver preneoplasia by diethylnitrosamine (DEN) in a sequential protocol of hepatocarcinogenesis, for three weeks male weanling rats were fed diets containing beta-carotene or canthaxanthin (300 mg/kg diet) or excess vitamin A (70,000 IU/kg diet) or were given beta-carotene by injection (9 injections at 10 mg/kg body wt ip). On Day 15, all rats were injected with 200 mg DEN/kg body wt ip; later they were submitted to 2-acetylaminofluorene treatment and to two-thirds hepatectomy, then to phenobarbital treatment, after which gamma-glutamyltranspeptidase- and placental glutathione-S-transferase-positive liver foci were histologically detected. Neither beta-carotene (fed or injected), canthaxanthin, nor an excess of dietary vitamin A had an influence on the number and size of preneoplastic liver foci, despite a significant incorporation and persistence in liver of both carotenoids, especially canthaxanthin, and of supplemental vitamin A. These results are in conflict with another report in which beta-carotene, given to rats during the initiation phase, was found to strongly inhibit DEN-induced hepatocarcinogenesis.
Astorg
P
P
Unité de Toxicologie Nutritionnelle, Institut National de la Recherche Agronomique, Dijon, France.
Gradelet
S
S
Bergès
R
R
Suschetet
M
M
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D016644:Canthaxanthin / Q000008:administration & dosage / Q000494:pharmacology*; D002273:Carcinogens; D004032:Diet; D004052:Diethylnitrosamine; D005982:Glutathione Transferase / Q000032:analysis; D008099:Liver / Q000201:enzymology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D019207:beta Carotene / Q000008:administration & dosage / Q000494:pharmacology*; D005723:gamma-Glutamyltransferase / Q000032:analysis
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D019207:beta Carotene; D004052:Diethylnitrosamine; D016644:Canthaxanthin; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase