COMPARATIVE STUDIES ON ANILINE HYDROXYLATION AND p-NITROTOLUENE HYDROXYLATION BY THE LIVER

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The question whether or not biotransformation of two drugs, especially hydroxylation, is catalyzed by one “drug-metabolizing enzyme” (1) inevitably arises when one considers possible changes in the effects due to metabolic modification by simultaneous administration of several drugs. Recently, evidence has accumulated toward the view that multiple oxidative enzymes are present in hepatic microsomes (2-9). It was found in our laboratory (10) that a wide difference exists in the magnitude of induction of hepatic activities between aniline hydroxylation (aryl 4-hydroxylase, EC 1.14.1.1) and p-nitrotoluene hydroxylation (EC1.14.1.0) when rats are pretreated with phenobarbital. This observation led us to speculate that the two compounds of closely related structures are hydroxylated by different enzymes. Although an exact comparison waits further progress in solubilization of hepatic microsomes (11, 12), an attempt is made in the present study to justify our hypothesis by comparative studies on hepatic activities between sexes and species of rodents as well as on the effects of inducers and inhibitors on the kinetics of the two hydroxylation activities.
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