DNA binding of N-hydroxy-Trp-P-2 and N-hydroxy-Glu-P-1 by acetyl-CoA dependent enzyme in mammalian liver cytosol

Abstract

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-l-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.