Alterations in Microsomal Metabolism of Benzo [a] pyrene in Mice Fed Butylated Hydroxyanisole2

Abstract

The metabolism of benzo[a]pyrene (BP) by liver microsomes in female A/HeJ mice fed a control diet or a diet containing butylated hydroxyanisole (BHA) was studied. Aryl hydrocarbon hydroxylase activity (AHH) was not changed by BHA feeding. However, the measurement of other parameters demonstrated that BHA feeding altered the microsomal system metabolizing BP. Incubation of BP and calf thymus DNA with liver microsomes from BHA-fed mice showed about half the binding of BP metabolites to DNA as compared to that of controls. The AHH activity of mice fed BHA was much more sensitive to in vitro inhibition by alpha-naphthoflavone than that of controls. The amount of cytochrome P450 was increased per unit weight of microsomal protein and liver in mice fed BHA. The ethyl isocyanide binding spectra were measured to see if alterations of cytochrome P450 might be produced by BHA feeding. The maximum at 430 nm was the same in control and BHA-fed mice. However, the maximum at 455 nm was lower in BHA-fed mice than in controls, which indicated that BHA had caused some changes. The data showed that BHA feeding resulted in altered properties of liver microsomes, including a decrease in BP metabolite binding to DNA.