DNA binding of N-hydroxy-Trp-P-2 and N-hydroxy-Glu-P-1 by acetyl-CoA dependent enzyme in mammalian liver cytosol.
3-Hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole and 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole, active metabolites of protein pyrolysate carcinogens, were further activated to DNA-binding species by an acetyl-CoA dependent enzyme in hepatic cytosol. This activity was supported also by N-hydroxy-2-acetylaminofluorene instead of acetyl-CoA, and it was inhibited by iodoacetamide and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) but not by diethyl-p-nitrophenylphosphate. The activity was observed in the cytosols of rats, mice and rapid acetylator rabbits, which possessed N-acetylation activity of 2-aminofluorene and Trp-P-2. On the other hand, the activity could not be detected in the cytosols of a dog and a slow acetylator rabbit.
D000105:Acetyl Coenzyme A / Q000494:pharmacology*; D000107:Acetylation; D000818:Animals; D002243:Carbolines / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology*; D004247:DNA / Q000378:metabolism*; D007093:Imidazoles / Q000378:metabolism*; D066298:In Vitro Techniques; D007211:Indoles / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D051379:Mice; D009153:Mutagens / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D013045:Species Specificity
D002243:Carbolines; D007093:Imidazoles; D007211:Indoles; D009153:Mutagens; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; D000105:Acetyl Coenzyme A; C027210:3-hydroxyamino-1-methyl-5H-pyrido(4,3-b)indole; D004247:DNA