No evidence for an inhibitory effect of β‐carotene or of canthaxanthin on the initiation of liver preneoplastic foci by diethylnitrosamine in the rat

Abstract

To test whether β‐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 β‐carotene or canthaxanthin (300 mg/kg diet) or excess vitamin A (70,000 IU/kg diet) or were given β‐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 γ‐glutamyltranspeptidase‐ and placental glutathione‐S‐transferase‐positive liver foci were histologically detected. Neither β‐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 β‐carotene, given to rats during the initiation phase, was found to strongly inhibit DEN‐induced hepatocarcinogenesis.