Dose-response studies on the induction of liver cytochromes P4501A1 and 1B1 by polycyclic aromatic hydrocarbons in arylhydrocarbon-responsive C57BL/6J mice

1. To determine the biological effects of 23 polycyclic aromatic hydrocarbons (PAHs) and 3,4,30,40-tetrachlorobiphenyl, the dose–response studies of the induction of CYP1- dependent xenobiotic oxidation activities by these chemicals in liver microsomes of C57BL/6J mice were studied. 2. In arylhydrocarbon-responsive C57BL/6J mice, the liver microsomal xenobiotic oxidation with substrates of 7-ethoxyresoru.n, 7-ethoxycoumarin, (±)-benzo[a]pyrene- 7,8-diol, dibenzo[a,l] pyrene-11,12-diol and 2-amino-3,5-dimethylimidazo[4,5-f]quinoline increased by increasing the doses of PAHs to mice, particularly when the PAHs that have been reported to be carcinogenic in experimental animals were used. In arylhydrocarbon receptor-knockout mice, there were no increases in liver microsomal 7-ethoxyresoru.n O-deethylation activities nor in liver mRNA levels of CYP1A1, 1A2 and 1B1 by these chemicals. 3. Of the chemicals examined, benzo[k].uoranthene, benzo[b].uoranthene, benzo [j] -. uoranthene, 3-methylcholanthrene, dibenz[a,...