Effects of 3-methylsulphonyl-4,5,3′,4′-tetrachlorobiphenyl and 7,8-benzoflavone on mouse liver aryl hydrocarbon hydroxylase activity in vitro

The activity of aryl hydrocarbon hydroxylase (AHH) in mouse liver microsomes was assayed in the presence of 3-methylsulphonyl-4,5,3′,4′-tetrachlorobiphenyl (3-MSF-TCB). The mice had been previously injected with a fixed amount of the AHH inducer 3-methylcholanthrene (MC) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or with the vehicle (olive oil) alone. The dose-effect patterns for 3-MSF-TCB were markedly different according to the genetic responsiveness of the mice towards aromatic hydrocarbons (Ah responsiveness); in Ah responsive strains 3-MSF-TCB inhibited the MC-induced AHH activity as did 7,8-benzoflavone (ANF), which is known to be a potent inhibitor of AHH, whereas in Ah non-responsive strains 3-MSF-TCB (and ANF) greatly enhanced the same activity. On the other hand, the dose-response patterns were similar for both types of mice for TCDD-induced activity or basal activity (mice injected with the vehicle alone). The dose-effect curves for 3-MSF-TCB were quite distinct from those for ANF, particularly with respect to the basal AHH activity, for both Ah responsive and non-responsive strains. These results indicate that both ANF and 3-MSF-TCB can have either an inhibitory or an activating effect on AHH, depending on the dose, the Ah phenotype and previous induction with MC or TCDD.