Rat lung and liver cytochrome P-450 isozymes involved in the hydroxylation of m-xylene.
The primary metabolism of m-xylene in rat lung and liver microsomes was investigated. The ratio of side chain to aromatic hydroxylation was found to be approximately 1:1 in lung microsomes from untreated rats and in a reconstituted system containing the major cytochrome P-450 isozyme induced in rat liver by phenobarbital, cytochrome P-450-PB-B2, as compared to 8:1 in liver microsomes. Antibody inhibition studies showed the major importance of cytochrome P-450-PB-B2 for the formation of both primary m-xylene metabolites (3-methylbenzylalcohol and 2,4-dimethylphenol) in lung microsomes. Antibodies to the major cytochrome P-450 isozyme induced in rat liver by beta-naphthoflavone, P-450-BNF-B2, did not inhibit m-xylene metabolism in either liver or lung microsomes from beta-naphthoflavone treated rats although this isozyme efficiently catalyzed m-xylene hydroxylation in a reconstituted system. m-Xylene metabolism by purified P-450-BNF-B2 appeared to cause rapid inactivation of the enzyme.
Toftgård
R
R
Haaparanta
T
T
Halpert
J
J
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000276:immunology / Q000378:metabolism*; D006900:Hydroxylation; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000201:enzymology / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014992:Xylenes / Q000378:metabolism*
D000906:Antibodies; D007527:Isoenzymes; D014992:Xylenes; D003577:Cytochrome P-450 Enzyme System; C031285:3-xylene