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Mutagenesis, Vol. 15, No. 3, 223-228, May 2000
© 2000 UK Environmental Mutagen Society/Oxford University Press

Protection against Trp-P-2 mutagenicity by purpurin: mechanism of in vitro antimutagenesis

Tim Marczylo*, Sakae Arimoto-Kobayashi and Hikoya Hayatsu

Faculty of Pharmaceutical Sciences, Okayama University, Tsushima naka 1-1-1, Okayama 700 8530, Japan

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 {omega}-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.

* To whom correspondence should be addressed. Present address: Edward Llwyd Building, University of Wales, Aberystwyth SY23 3DA, UK; Tel: +44 1970 621515; Fax: +44 1970 622350; Email: tom{at}aber.ac.uk


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