INHIBITION OF THE HEPATOCARCINOGENICITY OF AFLATOXIN B-1 IN RATS BY LOW-LEVELS OF THE PHENOLIC ANTIOXIDANTS BUTYLATED HYDROXYANISOLE AND BUTYLATED HYDROXYTOLUENE

The phenolic antioxidants butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) were studied for inhibition of aflatoxin B-1 (AF B(1)) hepatocarcinogenesis in male Fischer 344 rats. The antioxidants were administered at 5, 25, or 125 ppm in AIN-76A diet for 42 weeks. B eginning with week 2, 5 mu g/kg of AFB(1) was given by intragastric in stillation three times a week for 40 weeks either alone or concurrentl y with BHA or BHT feeding. The development of hepatocellular altered f oci (HAF) induced by AFB(1), as indicators of hepatocarcinogenesis, wa s monitored using immunohistochemical staining for the placental form of glutathione S-transferase. By 16 weeks the multiplicity of foci was 1.97/cm(2) of liver area in rats given only AFB(1), and this increase d to 4.11/cm(2) at 24 weeks and to 10.60/cm(2) at 32 weeks. At the fin al sacrifice at 42 weeks, the multiplicity of foci was 12.90/cm(2) com pared to 0.75/cm(2) in untreated controls. In rats given antioxidants in addition to AFB(1), the high dose of BHA reduced the multiplicity t o 7.72/cm(2) and the high dose of BHT reduced the multiplicity to 9.35 /cm(2). Lower levels did not reduce foci induction. Thus, in male rats under the conditions of this experiment, the level of 125 ppm of eith er BHA or BHT inhibited the initiation of hepatocarcinogenesis by AFB( 1). The BHA effect was slightly greater than that of BHT.