mechanismbased inactivation of cytochrome p450 1a1 by naralkyl1aminobenzotriazoles in guinea pig kidney in vivo and in vitro minimal effects on metabolism of arachidonic acid by renal p450dependent monooxygenases guinea pig renal microsomes convert arachidonic acid to two classes of p450dependent metabolites epoxyeicosatrienoic acids eet and 16 through 20hydroxyeicosatetraenoic acids 1620ohaa the rate of formation of these metabolites was not altered by betanaphthoflavone induction which increased p450 1a1dependent 7ethoxyresorufin odeethylation activity approximately 100fold alphanaphthoflavone which inhibits renal p450 1a1 in vitro did not inhibit the formation of these metabolites in microsomes from induced animals in induced animals nbenzyl1aminobenzotriazole and nalphamethylbenzyl1aminobenzotriazole administered iv inhibited microsomal 7ethoxyresorufin odeethylation activity by approximately 50 without inhibiting the formation of either class of arachidonic acid metabolites in vitro these mechanismbased inhibitors inactivated 1a1 by 90 without inhibiting eet or 1620ohaa formation these data show that p450 1a1 does not bioactivate arachidonic acid to either 1620ohaa or eet in guinea pig kidney and that nbenzyl1aminobenzotriazole and nalphamethylbenzyl1aminobenzotriazole selectively inactivate p450 1a1 in comparison to the p450 isozymes that metabolize arachidonic acid in the kidney in guinea pig liver betanaphthoflavone treatment which induces p450 1a1 and 1a2 increased the rate of the formation of 1620ohaa and eet and in vitro alphanaphthoflavone inhibited the formation of these metabolites in induced hepatic microsomes by approximately 50 and approximately 35 respectively these data demonstrate that a betanaphthoflavoneinducible isozyme most likely 1a2 converts arachidonic acid to both 1620ohaa and eet in guinea pig liver