Metabolic activation of trp-P-2, a mutagenic amine from tryptophan-pyrolysate, by liver microsomes from 3-methylcholanthrene-responsive and non-responsive mice.
1. The metabolic activation of a tryptophan pyrolysate, Trp-P-2 (3-amino-1-methyl-5H-pyrido[4,3-]indole), was studied using liver microsomes from mice of 3-methylcholanthrene-responsive, C57BL/6N (B6) strain and non-responsive, DBA/2N (D2) strain. 2. The formation of N-hydroxy-Trp-P-2 (3-hydroxylamino-1-methyl-5H-pyrido-[4,3-b]indole) by hepatic microsomes was markedly increased by the pretreatment with 3-methylcholanthrene in B6 mice, but not in D2 mice. 3. The same treatment increased the activity to convert Trp-P-2 to a mutagen(s) in the Salmonella/microsome test system in B6 mice, but not in D2 mice. 4. The formation of N-hydroxy-Trp-P-2 corresponded with the increase in the number of the revertants, and with the activities of aromatic hydrocarbon hydroxylase and biphenyl 2-hydroxylase. 5. Addition of alpha-naphthoflavone to microsomes from control and 3-methyl-cholanthrene-treated B6 mice effectively decreased the activities to convert Trp-P-2 to a mutagen(s) and to N-hydroxylate Trp-P-2. 6. These results indicate that N-hydroxy-Trp-P-2 is a proximate or ultimate mutagenic principle of Trp-P-2.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D002243:Carbolines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004790:Enzyme Induction; D007211:Indoles / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008862:Microsomes, Liver / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D009153:Mutagens / Q000378:metabolism*; D051381:Rats
D002243:Carbolines; D007211:Indoles; D009153:Mutagens; D008748:Methylcholanthrene; C027210:3-hydroxyamino-1-methyl-5H-pyrido(4,3-b)indole; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; D006899:Mixed Function Oxygenases; C027686:tryptophan pyrolysate N-hydroxylase; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; C021775:biphenyl-2-hydroxylase