LONG-TERM ADMINISTRATION OF TOCOTRIENOLS AND TUMOR-MARKER ENZYME-ACTIVITIES DURING HEPATOCARCINOGENESIS IN RATS

The effects of long-term administration of tocotrienol on hepatocarcin ogenesis in rats induced by diethylnitrosamine (DEN) and 2-acetylamino fluorene (AAF) were investigated by determining the activities of gamm a-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), glutathio ne S-transferases (GSTs), and glutathione (GSH) levels in blood and li ver. Twenty-eight male 7- to 8-wk-old Rattus norwegicus rats, weighing 120-160 g, were used in this study. The rats were divided into four t reatment groups: a control group on a basal diet, a group fed a basal diet supplemented with tocotrienol (30 mg/kg food), a group treated wi th DEN/AAF, and a group treated with DEN/AAF and fed a diet supplement ed with tocotrienol (30 mg/kg food). Blood was collected monthly, and GGT, ALP, and GSH levels were determined. The rats were killed after 9 mo, and the livers were examined morphologically. Grayish white nodul es (2/liver) were found in atl the DEN/AAF-treated rats (n = 10), but only one of the rats treated with DEN/AAF and supplemented with tocotr ienol (n = 6) had liver nodules. A significant increase in the level o f blood and liver GSH, ALP, and GGT activities was observed in the DEN /AAF-treated rats. Liver GSTs were similarly increased with DEN/AAF tr eatment. Tocotrienol supplementation attenuated the impact of the carc inogens in the rats.