Selective inhibition and kinetics of enzymatic reactions leading to irreversible binding of benzo[a]pyrene to microsomal macromolecules of mouse lung.
Two enzymatic reactions, catalyzed by mouse lung microsomes and distinguishable by selective inhibition and kinetic studies, lead to irreversible binding of benzo[a]pyrene to macromolecules present in vitro reaction systems. One type (low Km) is inducible in the lungs of mice by treatment with benz[a]anthracene and is subject to inhibition by 7,8-benzoflavone. The other type (high Km) is predominant in lungs of untreated mice, but a small amount of low-Km activity is also present. The high-Km activity may be involved in carcinogenesis by benzo[a]pyrene, for it is inhibited by butylated hydroxytoluene, retinol or disulfiram, each of which is reported to have anticarcinogenic activity in intact animals.
D000818:Animals; D001551:Benz(a)Anthracenes / Q000494:pharmacology; D001571:Benzoflavones / Q000494:pharmacology; D001580:Benzopyrenes / Q000378:metabolism*; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D004221:Disulfiram / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D014801:Vitamin A / Q000494:pharmacology
D001551:Benz(a)Anthracenes; D001571:Benzoflavones; D001580:Benzopyrenes; D014801:Vitamin A; D002084:Butylated Hydroxytoluene; D004221:Disulfiram