Induction and inhibition of pesticide-metabolizing enzymes: roles in synergism of pesticides and pesticide action

Abstract

Synergism of the toxic action of pesticides is discussed with particular emphasis on the methylenedioxyphenyl (benzodioxole) (MDP) synergists and on how studies of these compounds may relate to the general significance of pesticide synergism. MDP compounds function as both inhibitors and inducers of cytochrome P450 isoforms, the two processes proceeding, in vivo, at different rates. Inhibition is mediated through the formation of metabolite inhibitory complexes, and induction involves both aryl hydrocarbon (Ah)-dependent and Ah-independent mechanisms. The significance of this biphasic effect on multienzyme xenobiotic metabolizing systems is illustrated by considerations of the insecticide phorate.