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

Odd G. Nilsen, Rune Toftgård, Lars Eng, Jan-Ake Gustafsson

Research output: Contribution to journalArticle

9 Scopus citations

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 dilauroylphatidylcholine. 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 phenobarbital 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)P4,5- 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.

Original languageEnglish (US)
Pages (from-to)369-376
Number of pages8
JournalActa Pharmacologica et Toxicologica
Volume48
Issue number5
DOIs
StatePublished - Jan 1 1981

Keywords

  • Cytochrome P‐450
  • liver
  • rabbit
  • regio‐selectivity

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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