US EPA

2197488 

Technical Report 

Rat liver microsome-mediated binding to DNA of 3-amino-1-methyl-5H-pyrido(4,3-b)indole, a potent mutagen isolated from tryptophan pyrolysate 

Hashimoto, Y; Takeda, K; Shudo, K; Okamoto, T; Sugimura, T; Kosuge, T 

1978 

Yes 

Chemico-Biological Interactions
ISSN: 0009-2797
EISSN: 1872-7786 

HEEP/79/07253 

BIOL INTERACT 

1 

137-140 

English 

699188 

10.1016/0009-2797(78)90047-9 

WOS:A1978FV01800011 

HEEP COPYRIGHT: BIOL ABS. Potent mutagens were isolated from a tryptophan pyrolysate and identified as 3-amino-1,4-dimethyl- and 3-amino-1-methyl-5H-pyrido(4,3-b)indoles (Trp-P-1 and 2). Their structures are given. These amines showed quite potent frameshift type mutagenic activity on bacteria. The presence of S-9 mix from rat liver was necessary for this activity, indicating that these compounds were transformed metabolically to activated forms. The induction of mutagenesis of carcinogenesis may be closely related to the binding of the activated mutagens or carcinogens to nucleic acid and/or protein. This paper reports the binding of Trp-P-2 to DNA when incubated with microsomes from the liver of PCB(polychlorinated biphenyl)-treated rats. The radioactivity of Trp-P-2 was found to bind to DNA in the presence of rat liver microsomes. The binding was very tight and was not affected by reprecipitation, dialysis, or gel chromatography.