Influence of inducers and inhibitors of mixed-function oxidasts on benzo(a)pyrene binding to the DNA of rat liver nuclei.
Benzo(a)pyrene-conjugated DNA was isolated after benzo(a)pyrene was incubated in vitro with liver nuclei from control, phenobarbital-treated, and methylcholanthrene-treated rats and the reduced nicotinamide adenine dinucleotide phosphate-generating system. Aryl hydrocarbon hydroxylase, the levels of activity of which varied with the different nuclear systems, was highly specific in the activation of the benzo(a)pyrene to forms that bind to DNA. Sephadex LH-20 chromatography of the degreded DNA from liver nuclei of pretreated rats revealed an in vivo DNA-bound product  previously shown to be derived from 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide (Product A). The nuclei from phenobarbital-pretreated rats also contained a DNA-bound product corresponding to that derived from the binding of benzo(a)pyrene 4,5-oxide (Product C), but they completely lacked the DNA-bound product derived from futher metabolism of 0-hydroxybenzo(a)pyrene (Product D). In contrast, nuclei from methylcholanthrene-treated rats yielded large amounts of Product D. No bound products were found with the control nuclei. 7,8-Benzoflavone caused an 80% inhibition of benzo(a)pyrene binding to DNA in the nuclei of methylcholanthrene-pretreated rats, but it had no effect on control nuclei or those from phenobarbital-pretreated rats. It inhibited formation of Product A, but not Products B or C, in nuclei from phenobarbital-pretreated rats. With nuclei from methylcholanthrene-pretreated rats. With nuclei from methylcholanthrene-pretreated animals, 7,8-benzoflavone led to an overall loss of products, but small amounts of Products A and B persisted. 1,1,1-Trichloropropene 2,3-oxide strongly inhibited nuclear aryl hydrocarbon hydroxylase activity and the phenol fraction measured by thin-layer chromatography in all nuclear systems, but it significantly increased the benzo(a)pyrene binding in all nuclei. With nuclei from phenobarbital-treated rats, it inhibited the formation of Product B but not of Products A and C; whereas with nuclei from methylcholanthrene-pretreated rats, it inhibited the fromation of all the hydrocarbon-deoxyribonucleoside products.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001580:Benzopyrenes / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002852:Chromatography, Ion Exchange; D004988:Ethers, Cyclic / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006843:Hydrocarbons, Chlorinated / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008748:Methylcholanthrene / Q000494:pharmacology; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats
D001580:Benzopyrenes; D004988:Ethers, Cyclic; D005419:Flavonoids; D006843:Hydrocarbons, Chlorinated; D008748:Methylcholanthrene; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; D010634:Phenobarbital