Mutagenicities of nitrosated carboline derivatives.
Food-borne amines have been considered as the potential precursors of endogenous carcinogenic N-nitroso compounds in humans. A compound which yields a direct mutagen after nitrite treatment was isolated from soy sauce and was identified as 1-methyl-1,2,3,4-tetrahydro-2-carboline-3-carboxylic acid (MTCA) (Wakabayashi, et al., 1983). The mutagenicities of other carboline derivatives such as harman, norharman, harmaline, harmalol, harmine, and harmol were studied. Like MTCA, the nitrosated carboline derivatives showed higher mutagenic activity as compared to their corresponding parent compounds. The demethylated analogue of MTCA, 1,2,3,4-tetrahydro-2-carboline-3-carboxylic acid was synthesized and its nitrosated products were shown to be mutagenic to Salmonella typhimurium TA 100 and TA 98. The potent mutagen Trp-P-2 is a typical 3-carboline derivative. The mutagenicity of Trp-P-2 was suppressed remarkably after nitrosation. Several 3-carboline derivatives also showed the similar property. Nitrosation of MTCA gave several derivatives which were isolated and showed direct mutagenicity to Salmonella typhimurium TA 98. Further characterization of these new carboline derivatives is in progress.
D002243:Carbolines / Q000302:isolation & purification / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D004305:Dose-Response Relationship, Drug; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens; D009603:Nitroso Compounds / Q000378:metabolism; D012486:Salmonella typhimurium / Q000187:drug effects
D002243:Carbolines; D009153:Mutagens; D009603:Nitroso Compounds; C038114:1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid