Regio‐Selectivity of Purified Forms of Rabbit Liver Microsomal Cytochrome P‐450 in the Metabolism of Benzo(a)pyrene, n‐Hexane and 7‐Ethoxyresorufin

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Abstract
The specificity of electrophoretically homogeneous preparations of rabbit liver microsomal cytochrome P‐450lm2–4 towards oxygenation of n‐hexane, 7‐ethoxyresorufin and benzo(a)pyrene was examined using a reconstituted system consisting of cytochrome P‐450, NADPH‐cytochrome P‐450 reductase and dilauroylphosphatidylcholine. Epoxide hydrase was included when benzo(a)pyrene was used as substrate. Cytochrome P‐450lm2 was most active in n‐hexane and benzo(a)pyrene oxygenation especially with regard to the formation of 2‐hexanol, B(a)P‐4,5‐dihydrodiol and B(a)P‐phenol metabolites. 7‐Ethoxyresorufin was, however, a very poor substrate for cytochrome P‐450lm2. Cytochrome P‐450lm3 had less activity towards the investigated substrates while cytochrome P‐450lm4 preferentially formed 2‐ and 3‐hexanol, resorufin and B(a)P‐9,10‐dihydrodiol. Cytochrome P‐450lm4 isolated after pretreatment with 3‐methylcholanthrene or pheno‐barbital showed roughly the same characteristics except in the formation of 1‐hexanol where cytochrome P‐450lm4 isolated after phenobarbital treatment was the most effective. The formation of B(a)P‐4,5‐ and −9,10‐dihydrodiols was greatly increased by incorporation of epoxide hydrase. Our results indicate a certain specificity of the different forms of cytochrome P‐450 in the liver microsomes although some overlap in activities was observed.

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