SELECTIVE INDUCTION OF RAT-LIVER PHASE-II ENZYMES BY N-HETEROCYCLE ANALOGS OF PHENANTHRENE - A RESPONSE EXHIBITING HIGH CORRELATION BETWEENUDP-GLUCURONOSYLTRANSFERASE AND MICROSOMAL EPOXIDE HYDROLASE ACTIVITIES

1. Among nitrogen heterocycles based on the planar phenanthrene struct ure are three (1,7- and 4,7-phenanthroline and phenanthridine) which s electively increase rat hepatic phase 11 drug metabolizing enzyme acti vities without increasing cytochrome P450 concentration. Of six monoox ygenase activities investigated, only ethoxyresorufin dealkylase was r aised but this was only minor. 2. The detergent-activated UDP-glucuron osyltransferase activities towards morphine, 4-nitrophenol, and 1-naph thol were increased up to five-, three- and two-fold of control respec tively. Microsomal epoxide hydrolase activity towards cis-stilbene oxi de was increased up to three-fold and cytosolic glutathione S-transfer ase activity towards 1-chloro-2, 4-dinitrobenzene reached twice the co ntrol value. 3. Cytosolic 4-nitrophenol sulphotransferase activity was not increased by any compound and like some monooxygenase reactions, was decreased by 4,7- and 1,7-phenanthrolines. 4. 1, 10-Phenanthroline and two compounds which lack a heterocyclic nitrogen atom, (phenanthr ene and 9-phenanthrol), failed to elicit any induction of enzyme activ ities. 5. Changes in microsomal epoxide hydrolase activity showed high correlation (r = 0.97) with changes in UDP-glucuronosyltransferase (4 -nitrophenol) activity.