The influence of polycyclic aromatic hydrocarbons as inducers of monooxygenases on the metabolite profile of benz[a]anthracene in rat liver microsomes.
Microsomal oxidation of benz[a]anthracene (BaA) in rat liver has been shown to occur at various positions (1,2-, 3,4-, 5,6-, 8,9- and 10,11-position) by means of gas chromatography/mass spectrometry (GC/MS) and comparison with synthetic reference substances. In normal rats trans-5,6-, 8,9- and, mainly, 10,11-dihydrodiols have been detected as primary metabolites. The induction of monooxygenases by polycyclic aromatic hydrocarbon (PAH) results in a considerable change in the metabolite profile, since the 5,6- and 8,9-isomers become the main metabolites while the amount of 10,11-isomer is not increased. Simultaneously, the secondary metabolism to form triols and tetrols is induced. Phenobarbital as well as 'moderately inducing' PAH (pyrene, benzo[ghi]perylene, benzo[e]pyrene) induced the oxidation at 5,6- and 8,9-position, whereas almost all other compounds investigated, especially the benzofluoranthenes, additionally induced the oxidation at the 3,4-position forming the precursor of the ultimate carcinogen of BaA, 3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenz[a]anthracene, which was detected as its isomerisation product, the 2,3,4-triol.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D004790:Enzyme Induction; D008862:Microsomes, Liver / Q000201:enzymology*; D010084:Oxidation-Reduction; D011083:Polycyclic Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D001551:Benz(a)Anthracenes; D011083:Polycyclic Compounds; D001189:Aryl Hydrocarbon Hydroxylases