Species and strain differences in the butylated hydroxytoluene (BHT)-producing induction of hepatic drug oxidation enzymes.

Five week-old, Wistar-JCL male and female rats and C57BL/6N male mice given a 0.5% butylated hydroxytoluene (BHT)-containing diet for 6 days produced a marked increase in hepatic weight and microsomal protein content. However, the augmentations of cytochrome P-450 content and drug oxidation activities were much more significant, i.e. 2.5-fold and more than three-fold increases were observed on a body weight basis, respectively. BHT-induced cytochrome P-450 cannot be distinguished from phenobarbital (PB)-induced cytochrome in many respects we have examined: i.e. 1) a broad substrate specificity; 2) absence of the blue shift in the CO-binding difference spectrum; 3) no rise in the peak height ratio of ethylisocyanide difference spectrum; 4) absence of α-naphthoflavone inhibition of p-nitroanisole demethylase activity; 5) marked increases of 50, 000 and 54, 000 molecular weight polypeptides in SDS-polyacrylamide gel electrophoresis. However, the induction of 46, 000 molecular weight polypeptide by BHT in rats was more conspicuous than that by PB, and this induction was not observed in mice. In contrast to this marked induction, the administration of BHT to MC nonresponsive DBA/2N mice produced neither hepatic enlargement nor induction of cytochromes, but did produce an extremely high mortality.