title: A novel mutagen, 2-(5-hydroxy-4,6-dinitroindolyl) ethanol, formed in the reaction between 5-hydroxytryptamine and nitrite under acid conditions, especially in the presence of L-cysteine.
abstract: We examined the mutagenic activity of each of 29 amino acids mixed under acidic conditions with 5-hydroxytryptamine (5-HT) and nitrite using Salmonella typhimurium strain TA 100 with or without a metabolic activation system (S9 mix). The reaction mixture containing L-cysteine was strongly mutagenic without S9 mix. We subjected an ethyl acetate extract of the reaction mixture to HPLC, isolated a mutagenic component, and investigated its chemical structure by LC-mass spectrometry (MS), high-resolution fast atom bombardment (HRFAB)-MS, and 1H and 13C NMR. We identified the mutagen as 2-(5-hydroxy-4,6-dinitro-3-indolyl) ethanol (2HDIE). We injected 8 mg/kg 2HDIE i.p. into male ICR mice and found that the compound increased the frequency of micronuclei in peripheral reticulocytes. Our results suggest that 2HDIE might be formed in vivo by consumption of 5-HT, nitrite and L-cysteine in foods, and might act as a mutagen.
authors.affiliation: Graduate School of Nutritional and Environmental Sciences and 21st COE Program, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. masudas@smail.u-shizuoka-ken.ac.jp
authors.forename: Shuichi
authors.initials: S
authors.lastname: Masuda
authors.forename: Yumeko
authors.initials: Y
authors.lastname: Terashima
authors.forename: Hiromi
authors.initials: H
authors.lastname: Tan
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashizume
authors.forename: Chitose
authors.initials: C
authors.lastname: Sugiyama
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamada
authors.forename: Minako
authors.initials: M
authors.lastname: Ajioka
authors.forename: Osamu
authors.initials: O
authors.lastname: Sugimoto
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Terao
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Tanji
authors.forename: Shigenori
authors.initials: S
authors.lastname: Kumazawa
authors.forename: Naohide
authors.initials: N
authors.lastname: Kinae
mesh_terms: D000818:Animals; D003545:Cysteine / Q000737:chemistry* / Q000493:pharmacokinetics; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D048648:Macronucleus / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009153:Mutagens / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D009573:Nitrites / Q000737:chemistry* / Q000493:pharmacokinetics; D012156:Reticulocytes / Q000187:drug effects / Q000648:ultrastructure; D012486:Salmonella typhimurium / Q000187:drug effects; D012701:Serotonin / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: C508026:2-(5-hydroxy-4,6-dinitroindolyl)ethanol; D007211:Indoles; D009153:Mutagens; D009573:Nitrites; D012701:Serotonin; D003545:Cysteine