Role of hemin in the inhibition of mutagenic activity of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and other aminoazaarenes

Sakae Arimoto, Hikoya Hayatsu

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The mechanism of inhibition by hemin of the mutagenic activities of food pyrolysate aminoazaarenes, particularly that of Trp-P-2 (3-amino-1-methyl-5H-pyrido[4,3-b]indole), was investigated. Hemin efficiently inhibited the metabolic activation by S9 of Trp-P-2, as demonstrated by high performance liquid chromatographic analysis of the reaction mixtures in which Trp-P-2 had been treated with S9 in the presence or absence of hemin. N-Hydroxy-Trp-P-2, an activated form of Trp-P-2 having direct mutagenicity on Salmonella typhimurium TA98, undergoes spontaneous oxidative degradation in its aqueous solution, and the presence of hemin in the solution accelerated the degradation significatly. The presence of excess hemin with N-hydroxy-Trp-2 completely abolished the mutagenic activity of this mutagen towards Salmonella. A UV-visible spectroscopic study has suggested the formation of a complex between hemin and N-hydroxy-Trp-P-2. In support of thsi view, the fluorescence spectrum of a Trp-P-2 solution was quenched efficiency by the addition of hemin. These observations indicate that this complex formation plays a role in the observed multiple actions of hemin. Similar inhibitory actions of hemin on several other direct-acting aminoazaarene mutagens are also described, as well as the inhibition activities of protoporphyrin, chlorophyllin, biliverdin and bilirubin.

Original languageEnglish
Pages (from-to)217-226
Number of pages10
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume213
Issue number2
DOIs
Publication statusPublished - 1989

Fingerprint

Hemin
Mutagens
Biliverdine
3-amino-1-methyl-5H-pyrido(4,3-b)indole
Salmonella typhimurium
Bilirubin
Salmonella
Fluorescence
High Pressure Liquid Chromatography
Food

Keywords

  • Aminoazaarenes
  • Hemin
  • Heterocyclic amines
  • Porphyrins
  • Trp-P-2

ASJC Scopus subject areas

  • Molecular Biology
  • Health, Toxicology and Mutagenesis
  • Medicine(all)

Cite this

@article{c0b2d44e76514f5eb2c9867633a5984b,
title = "Role of hemin in the inhibition of mutagenic activity of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and other aminoazaarenes",
abstract = "The mechanism of inhibition by hemin of the mutagenic activities of food pyrolysate aminoazaarenes, particularly that of Trp-P-2 (3-amino-1-methyl-5H-pyrido[4,3-b]indole), was investigated. Hemin efficiently inhibited the metabolic activation by S9 of Trp-P-2, as demonstrated by high performance liquid chromatographic analysis of the reaction mixtures in which Trp-P-2 had been treated with S9 in the presence or absence of hemin. N-Hydroxy-Trp-P-2, an activated form of Trp-P-2 having direct mutagenicity on Salmonella typhimurium TA98, undergoes spontaneous oxidative degradation in its aqueous solution, and the presence of hemin in the solution accelerated the degradation significatly. The presence of excess hemin with N-hydroxy-Trp-2 completely abolished the mutagenic activity of this mutagen towards Salmonella. A UV-visible spectroscopic study has suggested the formation of a complex between hemin and N-hydroxy-Trp-P-2. In support of thsi view, the fluorescence spectrum of a Trp-P-2 solution was quenched efficiency by the addition of hemin. These observations indicate that this complex formation plays a role in the observed multiple actions of hemin. Similar inhibitory actions of hemin on several other direct-acting aminoazaarene mutagens are also described, as well as the inhibition activities of protoporphyrin, chlorophyllin, biliverdin and bilirubin.",
keywords = "Aminoazaarenes, Hemin, Heterocyclic amines, Porphyrins, Trp-P-2",
author = "Sakae Arimoto and Hikoya Hayatsu",
year = "1989",
doi = "10.1016/0027-5107(89)90153-X",
language = "English",
volume = "213",
pages = "217--226",
journal = "Mutation Research",
issn = "0027-5107",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Role of hemin in the inhibition of mutagenic activity of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and other aminoazaarenes

AU - Arimoto, Sakae

AU - Hayatsu, Hikoya

PY - 1989

Y1 - 1989

N2 - The mechanism of inhibition by hemin of the mutagenic activities of food pyrolysate aminoazaarenes, particularly that of Trp-P-2 (3-amino-1-methyl-5H-pyrido[4,3-b]indole), was investigated. Hemin efficiently inhibited the metabolic activation by S9 of Trp-P-2, as demonstrated by high performance liquid chromatographic analysis of the reaction mixtures in which Trp-P-2 had been treated with S9 in the presence or absence of hemin. N-Hydroxy-Trp-P-2, an activated form of Trp-P-2 having direct mutagenicity on Salmonella typhimurium TA98, undergoes spontaneous oxidative degradation in its aqueous solution, and the presence of hemin in the solution accelerated the degradation significatly. The presence of excess hemin with N-hydroxy-Trp-2 completely abolished the mutagenic activity of this mutagen towards Salmonella. A UV-visible spectroscopic study has suggested the formation of a complex between hemin and N-hydroxy-Trp-P-2. In support of thsi view, the fluorescence spectrum of a Trp-P-2 solution was quenched efficiency by the addition of hemin. These observations indicate that this complex formation plays a role in the observed multiple actions of hemin. Similar inhibitory actions of hemin on several other direct-acting aminoazaarene mutagens are also described, as well as the inhibition activities of protoporphyrin, chlorophyllin, biliverdin and bilirubin.

AB - The mechanism of inhibition by hemin of the mutagenic activities of food pyrolysate aminoazaarenes, particularly that of Trp-P-2 (3-amino-1-methyl-5H-pyrido[4,3-b]indole), was investigated. Hemin efficiently inhibited the metabolic activation by S9 of Trp-P-2, as demonstrated by high performance liquid chromatographic analysis of the reaction mixtures in which Trp-P-2 had been treated with S9 in the presence or absence of hemin. N-Hydroxy-Trp-P-2, an activated form of Trp-P-2 having direct mutagenicity on Salmonella typhimurium TA98, undergoes spontaneous oxidative degradation in its aqueous solution, and the presence of hemin in the solution accelerated the degradation significatly. The presence of excess hemin with N-hydroxy-Trp-2 completely abolished the mutagenic activity of this mutagen towards Salmonella. A UV-visible spectroscopic study has suggested the formation of a complex between hemin and N-hydroxy-Trp-P-2. In support of thsi view, the fluorescence spectrum of a Trp-P-2 solution was quenched efficiency by the addition of hemin. These observations indicate that this complex formation plays a role in the observed multiple actions of hemin. Similar inhibitory actions of hemin on several other direct-acting aminoazaarene mutagens are also described, as well as the inhibition activities of protoporphyrin, chlorophyllin, biliverdin and bilirubin.

KW - Aminoazaarenes

KW - Hemin

KW - Heterocyclic amines

KW - Porphyrins

KW - Trp-P-2

UR - http://www.scopus.com/inward/record.url?scp=0024311654&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024311654&partnerID=8YFLogxK

U2 - 10.1016/0027-5107(89)90153-X

DO - 10.1016/0027-5107(89)90153-X

M3 - Article

C2 - 2668748

AN - SCOPUS:0024311654

VL - 213

SP - 217

EP - 226

JO - Mutation Research

JF - Mutation Research

SN - 0027-5107

IS - 2

ER -