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.
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.
Masuda
Shuichi
S
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
Terashima
Yumeko
Y
Tan
Hiromi
H
Hashizume
Takashi
T
Sugiyama
Chitose
C
Yamada
Shigeru
S
Ajioka
Minako
M
Sugimoto
Osamu
O
Terao
Yoshiyasu
Y
Tanji
Ken-ichi
K
Kumazawa
Shigenori
S
Kinae
Naohide
N
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
C508026:2-(5-hydroxy-4,6-dinitroindolyl)ethanol; D007211:Indoles; D009153:Mutagens; D009573:Nitrites; D012701:Serotonin; D003545:Cysteine