Methylenedioxyphenyl compounds as inducers of cytochrome P-450 and monooxygenase activity in the southern armyworm (Spodoptera eridania) and the rat

Exposure of sixth-instar southern armyworm larvae (Spodoptera eridania) to each of five methylenedioxphenyl (MDP) compounds (0.05%, w/v in the diet) led to increased levels of cytochrome P-450 and aryl hydrocarbon (benzo[a]pyrene) hydroxylase (AHH) activity in preparations of midgut microsomes. Isosafrole, the most potent compound evaluated, resulted in AHH levels almost 30-fold higher than in controls; it also enhanced levels of ethoxycoumarin O-deethylase activity (∼ 15-fold) but did not induce ethoxyresorufin O-deethylase or aldrin epoxidase. MDP-induced AHH activity was highly sensitive to inhibition by α-naphthoflavone (I50 = 0.4 μM) but was not inhibited by 1-phenylimidazole at 150 μM. Analysis of the major metabolites of benzo[a]pyrene in control and isosafrole-induced midgut microsomes established that MDP compounds promote the formation of the 3-hydroxy, 9-hydroxy, and 7,8-dihydrodihydroxy metabolites. In contrast, the metabolite pattern resulting from pentamethylbenzene induction indicated enhanced formation of the 9,10-dihydrodiol of benzo[a]pyrene. These metabolite patterns indicate the presence of armyworm midguts of distinct isozymes with different regiospecifities toward benzo[a]pyrene, and establish that the isozymes are different from those present in hepatic microsomes from control and phenobarbital-, β-naphthoflavone-, and dihydrosafrole-induced rats.