Comparison of the effect of low- and high-dose dietary butylated hydroxytoluene on microsome-mediated aflatoxin B1-DNA binding

Butylated hydroxytoluene (BHT) is known to inhibit tumor formation due to several chemical carcinogens including aflatoxin B1 (AFB1). Pre-treatment of laboratory animals with high doses of BHT (0.75% for 15 days in diet) is associated with pathological effects. The mechanism of action of BHT against AFB1 carcinogenesis is by induction of liver glutathione (GSH) S-transferases. As a result, the formation of AFB1-DNA binding is effectively inhibited. In the present study, effects of low and high doses of dietary BHT on in vitro activation and inactivation of AFB1 was examined. BHT feeding to rats at a dose of 0.75% for 15 days caused a significant increase in the GSH S-transferase activity. Addition of liver cytosolic fractions prepared from the rats pre-treated with high dose BHT to the cell free system caused a 48% inhibition in AFB1-DNA binding. In contrast, low dose BHT feeding (0.06% for 6 months) had little influence on GSH S-transferase activity. This was corroborated when addition of liver cytosol from low dose BHT-treated rats failed to inhibit microsome-mediated AFB1-DNA binding as compared to that of control. It is concluded that the permitted dose of BHT, added to processed food as preservative, plays no role in the biotransformation of AFB1.