Iron-chlorophyllin-mediated conversion of 3-hydroxyamino-1-methyl-5H- pyrido[4,3-b]indole (Trp-P-2(NHOH)) into its nitroso derivative

Sakae Arimoto, Naomi Inada, Hiromi Nakano, Haruki Rai, Hikoya Hayatsu

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Early work from our laboratory has shown that the mutagenicity of heterocyclic amines in Salmonella can be inhibited by hemin and chlorophyllins. We have speculated that the inhibition is a result of complex formation between heterocyclic amines and the pigments, and the speculation has been given a line of experimental evidence. We have now found that ferric-chlorophyllin (Fe-chlorophyllin) can modify the mutagenicity of 3- hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2(NHOH)), a metabolically activated form of 3-amino-1-methyl-SH-pyrido[4,3-b]indole (Trp-P-2). The mutagenicity of Trp-P-2(NHOH) in Salmonella typhimurium TA 98 (without S9) was strongly inhibited by an addition of an equimolar Fe-chlorophyllin in the pre-incubation mixture. Fe-chlorophyllin also inhibited the mutagenicity of 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d] imidazole (Glu-P-1(NHOH)). A rapid change in the UV spectrum of a mixture of Trp-P-2(NHOH) and Fe- chlorophyllin was observed. Analysis by high performance liquid chromatography showed that Trp-P-2(NHOH) was converted into 3-nitroso-1- methyl-5H-pyrido[4,3-b]indole (Trp-P-2(NO)), the mutagenic potency of which is a quarter of that of Trp-P-2(NHOH). Furthermore, the mutagenicity of Trp- P-2(NO), in turn, was inhibited by Fe-chlorophyllin. We conclude that the suppression of the mutagenicity of Trp-P-2(NHOH) is ascribable to the oxidative function of Fe-chlorophyllin, coupled with its ability to form complex formation with the planar surface of the heterocyclic amine molecules.

Original languageEnglish
Pages (from-to)259-269
Number of pages11
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume400
Issue number1-2
DOIs
Publication statusPublished - May 25 1998

Fingerprint

Iron
Amines
Carbolines
2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole
3-amino-1-methyl-5H-pyrido(4,3-b)indole
3-hydroxyamino-1-methyl-5H-pyrido(4,3-b)indole
chlorophyllin
Hemin
Salmonella typhimurium
Salmonella
High Pressure Liquid Chromatography

Keywords

  • Antimutagenicity
  • Chlorophyllin
  • Food pyrolysate mutagen
  • Inhibition of mutagenicity
  • Superoxide dismutase-like action
  • Trp-P- 2(NHOH)

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Molecular Biology

Cite this

Iron-chlorophyllin-mediated conversion of 3-hydroxyamino-1-methyl-5H- pyrido[4,3-b]indole (Trp-P-2(NHOH)) into its nitroso derivative. / Arimoto, Sakae; Inada, Naomi; Nakano, Hiromi; Rai, Haruki; Hayatsu, Hikoya.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 400, No. 1-2, 25.05.1998, p. 259-269.

Research output: Contribution to journalArticle

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AU - Arimoto, Sakae

AU - Inada, Naomi

AU - Nakano, Hiromi

AU - Rai, Haruki

AU - Hayatsu, Hikoya

PY - 1998/5/25

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N2 - Early work from our laboratory has shown that the mutagenicity of heterocyclic amines in Salmonella can be inhibited by hemin and chlorophyllins. We have speculated that the inhibition is a result of complex formation between heterocyclic amines and the pigments, and the speculation has been given a line of experimental evidence. We have now found that ferric-chlorophyllin (Fe-chlorophyllin) can modify the mutagenicity of 3- hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2(NHOH)), a metabolically activated form of 3-amino-1-methyl-SH-pyrido[4,3-b]indole (Trp-P-2). The mutagenicity of Trp-P-2(NHOH) in Salmonella typhimurium TA 98 (without S9) was strongly inhibited by an addition of an equimolar Fe-chlorophyllin in the pre-incubation mixture. Fe-chlorophyllin also inhibited the mutagenicity of 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d] imidazole (Glu-P-1(NHOH)). A rapid change in the UV spectrum of a mixture of Trp-P-2(NHOH) and Fe- chlorophyllin was observed. Analysis by high performance liquid chromatography showed that Trp-P-2(NHOH) was converted into 3-nitroso-1- methyl-5H-pyrido[4,3-b]indole (Trp-P-2(NO)), the mutagenic potency of which is a quarter of that of Trp-P-2(NHOH). Furthermore, the mutagenicity of Trp- P-2(NO), in turn, was inhibited by Fe-chlorophyllin. We conclude that the suppression of the mutagenicity of Trp-P-2(NHOH) is ascribable to the oxidative function of Fe-chlorophyllin, coupled with its ability to form complex formation with the planar surface of the heterocyclic amine molecules.

AB - Early work from our laboratory has shown that the mutagenicity of heterocyclic amines in Salmonella can be inhibited by hemin and chlorophyllins. We have speculated that the inhibition is a result of complex formation between heterocyclic amines and the pigments, and the speculation has been given a line of experimental evidence. We have now found that ferric-chlorophyllin (Fe-chlorophyllin) can modify the mutagenicity of 3- hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2(NHOH)), a metabolically activated form of 3-amino-1-methyl-SH-pyrido[4,3-b]indole (Trp-P-2). The mutagenicity of Trp-P-2(NHOH) in Salmonella typhimurium TA 98 (without S9) was strongly inhibited by an addition of an equimolar Fe-chlorophyllin in the pre-incubation mixture. Fe-chlorophyllin also inhibited the mutagenicity of 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d] imidazole (Glu-P-1(NHOH)). A rapid change in the UV spectrum of a mixture of Trp-P-2(NHOH) and Fe- chlorophyllin was observed. Analysis by high performance liquid chromatography showed that Trp-P-2(NHOH) was converted into 3-nitroso-1- methyl-5H-pyrido[4,3-b]indole (Trp-P-2(NO)), the mutagenic potency of which is a quarter of that of Trp-P-2(NHOH). Furthermore, the mutagenicity of Trp- P-2(NO), in turn, was inhibited by Fe-chlorophyllin. We conclude that the suppression of the mutagenicity of Trp-P-2(NHOH) is ascribable to the oxidative function of Fe-chlorophyllin, coupled with its ability to form complex formation with the planar surface of the heterocyclic amine molecules.

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KW - Chlorophyllin

KW - Food pyrolysate mutagen

KW - Inhibition of mutagenicity

KW - Superoxide dismutase-like action

KW - Trp-P- 2(NHOH)

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