INHIBITORY EFFECT OF BETA-CAROTENE ON CHRONIC 2-ACETYLAMINOFLUORENE INDUCED HEPATOCARCINOGENESIS IN RAT - REFLECTION IN HEPATIC DRUG-METABOLISM

The dietary administration of beta-carotene (BC; 100 mg/kg food) daily has been found to be highly effective in reducing cancer incidence in male Sprague-Dawley rats fed 2-acetyl-aminofluorene (0.05% in food). BC treatment either before initiation, during initiation and selection/promotion phases of hepatocarcinogenesis have been found to be effective in elevating hepatic microsomal cytochrome b(5) (24-50%), P-450 (18-38.5%), NADPH cytochrome c reductase (17.5-43.25%) and cytosolic aryl hydrocarbon hydroxylase (60.5-63.5%) activity to a statistically significant level measured either in the hyperplastic nodule (HN) or in the non nodular surrounding liver parenchyma (NNSP) compared to carcinogen control. Moreover, BC treatment throughout the study decrease the cytosolic 1-chloro-2,4-dinitrobenzene conjugated glutathione S-transferase (38.9-51.22%) and microsomal UDP-glucuronyl transferase (37.3-59.1%) activities to a significant level when compared to carcinogen control rats. A decrease in the number of hyperplastic nodules and their total liver parenchyma occupied were also observed in BC treated groups. Furthermore, a direct correlation between HNs and NNSP liver areas were observed with the hepatic Be and vitamin A contents and also with the rates and patterns of hepatic drug metabolism. Our results confirm the fact that BC is particularly protective in limiting the action of 2-AAF during the initiation phase of hepatocarcinogenesis.