Metabolic activation of 3-amino-5H-pyrido[4,3-b]indole, a highly mutagenic principle in tryptophan pyrolysate, by rat liver enzymes.
3-Amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), a mutagenic principle in tryptophan pyrolysates, binds to DNA after metabolic activation by rat liver enzymes. The enzymes for activation of Trp-P-2 were found in both microsomes and the cytosol. The reaction required NADPH and ATP, metabolic and was inhibited by 7,8-benzoflavone. Considerable binding was observed with only microsomes as enzyme source, but further addition of cytosol enhanced the binding, enhancement depending on the amount of cytosol added. Inducers for microsomal mixed-function oxidases induced activating enzyme(s) for Trp-P-2, 3-methylcholanthrene being most effective, followed by polychlorinated biphenyls and then phenobarbital.
D000818:Animals; D001711:Biotransformation; D002243:Carbolines / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D004247:DNA / Q000378:metabolism*; D004790:Enzyme Induction; D007211:Indoles / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009153:Mutagens / Q000378:metabolism*; D051381:Rats
D002243:Carbolines; D007211:Indoles; D009153:Mutagens; D004247:DNA