Isolation and Identification of a Novel Aromatic Amine Mutagen Produced by the Maillard Reaction

• Published in: Chemical research in toxicology 2009-09, Vol.22 (9), p.1588-1593
• Main Authors: Nishigaki, Rena, Watanabe, Tetsushi, Kajimoto, Tetsuya, Tada, Atsuko, Takamura-Enya, Takeji, Enomoto, Shigeki, Nukaya, Haruo, Terao, Yoshiyasu, Muroyama, Atsushi, Ozeki, Minoru, Node, Manabu, Hasei, Tomohiro, Totsuka, Yukari, Wakabayashi, Keiji
• Format: Article
• Language: English
• Subjects: Amines - chemistry; Amines - isolation & purification; Benzazepines - chemical synthesis; Benzazepines - chemistry; Benzazepines - isolation & purification; Chromatography, High Pressure Liquid; Hydroxyl Radical - metabolism; Hydroxyquinolines - chemical synthesis; Hydroxyquinolines - chemistry; Hydroxyquinolines - isolation & purification; Magnetic Resonance Spectroscopy; Maillard Reaction; Mutagenicity Tests; Mutagens - chemical synthesis; Mutagens - chemistry; Mutagens - isolation & purification; Salmonella typhimurium
• ISSN: 0893-228X; 1520-5010
• DOI: 10.1021/tx900119j

To clarify the formation of mutagens in the Maillard reaction of glucose and amino acids, 20 amino acids were separately incubated with glucose in the presence or absence of hydroxyl radicals produced by the Fenton reaction. After 1 week at 37 °C and pH 7.4, the reaction mixtures of glucose and tryptophan with and without the Fenton reagent showed mutagenicity toward Salmonella typhimurium YG1024 in the presence of a mammalian metabolic system (S9 mix). To identify mutagens in the reaction mixture, blue rayon-adsorbed material from a mixture of glucose, tryptophan, and the Fenton reagent was separated by column chromatography using various solid and mobile phases, and one mutagen, which accounted for 18% of the total mutagenicity of the reaction mixture, was isolated. The chemical structure of the mutagen was determined to be 5-amino-6-hydroxy-8H-benzo[6,7]azepino[5,4,3-de]quinolin-7-one (ABAQ) on the basis of ESI mass, high-resolution APCI mass, 1H NMR, 13C NMR, and IR spectral analyses and chemical synthesis of the mutagen. The novel aromatic amine showed high mutagenicity toward S. typhimurium TA98 and YG1024 with S9 mix, inducing 857 revertants of TA98 and 6007 revertants of YG1024/μg, respectively. The mutagenicity of ABAQ was comparable to that of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, which is a mutagenic and carcinogenic hetrocyclic amine in cooked meat and fish formed through the Maillard reaction at high temperature.