Brain microsomal enzyme mediated covalent binding of benzo[a]pyrene to DNA

The covalent binding of benzo[a]pyrene (BP) to calf thymus DNA by brain microsomes isolated from control and 3-methylcholanthrene (3-MC) treated rats was investigated. The influence of incubation time, pH, and concentrations of protein, BP and NADPH on covalent binding was investigated to obtain optimum conditions for the in vitro binding of [3H]BP to DNA. Treatment of rats to 3-MC resulted in a 1.53-fold increase in the brain microsomal mediated covalent binding of [3H]BP to DNA. Inhibitors of monooxygenase enzyme activity such as alpha-naphthoflavone, metyrapone, 1-benzylimidazole and ellagic acid significantly inhibited the binding of [3H]BP to DNA from control and 3-MC stimulated brain microsomes. Our results indicate that inhibitors and inducers of monooxygenases may modulate brain enzyme-mediated binding of polycyclic aromatic hydrocarbons (PAHs) to DNA.