Protection against Trp-P-2 mutagenicity by purpurin

Mechanism of in vitro antimutagenesis

Tim Marczylo, Sakae Arimoto, Hikoya Hayatsu

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Purpurin (1,2,4-trihydroxy-9,10-anthraquinone) is a natural pigment isolated from madder root (Rubia tinctorum) which inhibits the mutagenicity of a number of heterocyclic amines in the Ames mutagenicity test. Two effects were observed in the presence of purpurin. The rate of degradation of 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole [Trp-P- 2(NHOH)] at neutral pH was increased. The major product of this purpurin- dependent degradation was identified as the parent amine 3-amino-1-methyl- 5H-pyrido[4,3-b]indole (Trp-P-2). Secondly, the rate of Trp-P-2 N- hydroxylation, the major route of bioactivation, by PCB-treated rat hepatic microsomes was markedly decreased. Cytochrome P450-dependent O- dealkylation of methoxy-, ethoxy- and pentoxyresorufin by these microsomes was also significantly inhibited by purpurin. The nature of this inhibition was competitive. Spectrophotometric investigations suggest no direct interaction between Trp-P-2 and purpurin. Furthermore, no evidence for Trp-P-2 binding was observed with carminic acid, a structural analog of purpurin, when it was immobilized on ω-aminohexyl agarose. Therefore, in vitro the proposed mechanism by which purpurin protects against heterocyclic amine-induced mutagenesis involves competitive inhibition of cytochrome P450-dependent bioactivation and accelerated degradation of the N-hydroxylamine to the parent amine.

Original languageEnglish
Pages (from-to)223-228
Number of pages6
JournalMutagenesis
Volume15
Issue number3
Publication statusPublished - 2000

Fingerprint

Amines
Microsomes
Degradation
Cytochrome P-450 Enzyme System
Rubia
Carmine
Mutagenicity Tests
Dealkylation
Hydroxylation
Mutagenesis
Hydroxylamine
Polychlorinated Biphenyls
In Vitro Techniques
3-amino-1-methyl-5H-pyrido(4,3-b)indole
purpurin
Pigments
Sepharose
Rats
Liver

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Protection against Trp-P-2 mutagenicity by purpurin : Mechanism of in vitro antimutagenesis. / Marczylo, Tim; Arimoto, Sakae; Hayatsu, Hikoya.

In: Mutagenesis, Vol. 15, No. 3, 2000, p. 223-228.

Research output: Contribution to journalArticle

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