Cytochrome P450-dependent alkoxyphenoxazone dealkylase activities in lung microsomes from untreated and beta-naphthoflavone-treated rats: effect of in vitro inhibitors.
The reactivities of four alkoxyphenoxazone derivatives toward cytochrome P450-dependent monooxygenase activity were studied in lung microsomes from control and beta-naphthoflavone (BNF)-treated rats. Ethoxyphenoxazone (EtOPh)- and methoxyphenoxazone (MeOPh)-dealkylases were induced by beta NF (16- and 3.9-fold respectively), whereas benzyloxyphenoxazone (BzOPh)- and pentoxyphenoxazone (PeOPh)-dealkylase activities were unchanged after pre-treatment with beta NF. The specific activities of BzOPh'ase from control- and beta NF-treated rats and EtOPh'ase from beta NF-treated rats were sufficiently high (214-560 pmoles resorufin per min per mg protein) for routine biochemical studies. Each differed in its sensitivity toward the in vitro inhibitors, alpha-naphthoflavone (ANF) and metyrapone (MP). In lung microsomes from beta NF-treated rats the I50 (MP) = 7.6 X 10(-5) M for EtOPh'ase and 1.0 X 10(-6) M for BzOPh'ase. I50 (ANF) = 3.8 X 10(-8) M for EtOPh'ase. I50 (ANF) for BzOPh'ase could not be determined; at the highest concentration of ANF (10(-3) M), 50% inhibition was not observed. The presence of high levels of two distinct forms of lung microsomal P450-dependent alkoxyphenoxazone dealkylases, BzOPh'ase from untreated and beta NF-treated rats and EtOPh'ase from beta NF-treated rats, will be useful for studies on specific P450-xenobiotic interactions in rat pulmonary tissue.
Rabovsky
J
J
Division of Respiratory Disease Studies, National Institute for Occupational Safety & Health, Morgantown, WV 26505.
Judy
D J
DJ
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D003640:Dealkylation; D005419:Flavonoids / Q000494:pharmacology*; D066298:In Vitro Techniques; D008168:Lung / Q000201:enzymology*; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D008861:Microsomes / Q000201:enzymology*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D005419:Flavonoids; C011512:alpha-naphthoflavone; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D008797:Metyrapone