INHIBITORY EFFECTS OF BETA-CAROTENE ON PRENEOPLASTIC LESIONS INDUCED IN WISTAR RATS BY THE RESISTANT HEPATOCYTE MODEL

The inhibitory effects of beta-carotene (BC) on preneoplastic lesions induced in male Wistar rats by the resistant hepatocyte model was investigated. Rats were divided into six groups. Initiation was performed in all animals by a single injection of diethylnitrosamine. During the selection/promotion period five doses of 2-acetylaminofluorene were administered to the rats and a partial hepatectomy was performed. To three different groups BC was given by gavage throughout the experiment, before the initiation or during the selection/promotion period respectively. Three other groups served as controls and received corn oil instead of the carotenoid. At the end of the study (8 weeks), BC administration throughout the experiment reduced the incidence (P < 0.005), multiplicity as well as the total number and size of hepatocyte nodules. Furthermore, it significantly decreased the number of foci per cm2 (p < 0.05), the average focal area (P < 0.01) and the percentage of liver parenchyma occupied (P < 0.01). Similar results were observed when BC was given only before the initiation. However, the administration of the carotenoid during the selection/promotion period did not result in significant decreases of these parameters. These results suggest that the inhibitory effects of BC are primarily exerted on the initiation phase of the hepatocarcinogenic process. Nevertheless, continuous long-term exposure to the carotenoid would confer a greater degree of protection. In addition, by means of an analysis of correlation a positive relationship was found between the number of hepatocyte nodules and the hepatic concentration of BC. In contrast, an inverse relationship was observed between the number of nodules and the hepatic concentration of total vitamin A.