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Abstract
1. Among nitrogen heterocycles based on the planar phenanthrene structure are three (1,7- and 4,7-phenanthroline and phenanthridine) which selectively increase rat hepatic phase II drug metabolizing enzyme activities without increasing cytochrome P450 concentration. Of six monooxygenase activities investigated, only ethoxyresorufin dealky-lase was raised but this was only minor.
2. The detergent-activated UDP-glucuronosyltransferase activities towards morphine, 4-nitrophenol, and 1-naphthol were increased up to five-, three- and two-fold of control respectively. Microsomal epoxide hydrolase activity towards cis-stilbene oxide was increased up to three-fold and cytosolic glutathione S-transferase activity towards 1-chloro-2, 4-dinitrobenzene reached twice the control 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, (phenanthrene and 9-phenanthrol), failed to elicit any induction of enzyme activities.
5. Changes in microsomal epoxide hydrolase activity showed high correlation (r=0.97) with changes in UDP-glucuronosyltransferase (4-nitrophenol) activity.