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. © 1979.