Binding of quinoline to nucleic acid in a subcellular microsomal system.
Quinoline, a hepatocarcinogen in rats and mutagen in Salmonella typhimurium, binds to RNA, DNA and certain polyribonucleotides in the presence of NADPH and rat liver microsomes. The binding was pronounced with the help of liver microsome preparations made from the rats pretreated with some inducers of the microsomal monooxygenase system. The binding reaction required NADPH and was inhibited by carbon monoxide or aniline, and also by 7,8-benzoflavone, methyrapone or SKF 525A. These results suggested that the cytochrome P-450-linked monooxygenase system is involved in this binding process. Quinoline bound preferably to poly(A), poly(C), poly(G) and poly(X), but negligibly to poly(U) and poly(I). Most of the quinoline residues of the adducts, regardless of the kind of polynucleotides used, were released by acid or alkali at 100 degrees C in the form of 3-hydroxyquinoline. This suggests that 2,3- or 3,4-epoxy derivative of quinoline is the reactive intermediate for nucleic acid modification.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004790:Enzyme Induction; D006912:Hydroxyquinolines / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009249:NADP / Q000494:pharmacology; D009696:Nucleic Acids / Q000378:metabolism*; D010105:Oxygenases / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000494:pharmacology; D011131:Polyribonucleotides / Q000378:metabolism*; D011804:Quinolines / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship
D006912:Hydroxyquinolines; D009696:Nucleic Acids; D011131:Polyribonucleotides; D011804:Quinolines; D009249:NADP; D012313:RNA; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D010105:Oxygenases