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 to 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.