The influence of microsomal and nuclear aryl hydrocarbon hydroxylase (AHH) activity on the covalent binding of [G-3H]benzo(a)pyrene to rat liver DNA was evaluated in vivo. Induction of microsomal AHH was obtained after phenobarbital treatment (160% of control), which also increased DNA binding to 190%, but left the nuclear activity unchanged. Nuclear AHH was induced with dieldrin (150%), and the binding was decreased to 75%, whereas the microsomal AHH was at control level. The increasing effect of microsomal AHH induction as well as the decreasing effect of nuclear AHH induction on the binding was shown clearly when the data of the individual rats were used to solve the equation Binding = a*(microsomal AHH) + b*(nuclear AHH) + c multiple linear regression analysis with the data from 10 animals resulted in positive values for a and c, a negative value for b, and a good multiple correlation coefficient of r = 0.974. Pretreatment with 3-methylcholanthrene induced microsomal AHH to 380% of control and nuclear AHH to 590% and increased the binding to 175%. The binding was higher than predicted by the formula found, probably because the increasing influence of induced microsomal AHH overshadowed the decreasing effect of the nuclear AHH. The study shows clearly that the binding of a foreign compound to DNA in vivo is dependent not only on microsomal enzyme activities but also on nuclear activities even if the latter are considerably lower than those of microsomes.
Part of this work has been presented at the 10th Annual Meeting of the Union of the Swiss Societies for Experimental Biology, Davos, Switzerland, May 19 to 20, 1978, and at the 20th Congress of the European Society of Toxicology, Berlin, GFR, June 25 to 28, 1978.