Iron-chlorophyllin-mediated conversion of 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2(NHOH)) into its nitroso derivative.
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-5H-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.
Arimoto-Kobayashi
S
S
Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima, Okayama 700, Japan. arimoto@cc.okayama-u.ac.jp
Inada
N
N
Nakano
H
H
Rai
H
H
Hayatsu
H
H
D000332:Aerobiosis; D016587:Antimutagenic Agents / Q000494:pharmacology*; D002243:Carbolines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002735:Chlorophyllides / Q000494:pharmacology*; D007501:Iron / Q000494:pharmacology*; D009152:Mutagenicity Tests; D009603:Nitroso Compounds / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics / Q000254:growth & development
D016587:Antimutagenic Agents; D002243:Carbolines; D002735:Chlorophyllides; D009603:Nitroso Compounds; C027210:3-hydroxyamino-1-methyl-5H-pyrido(4,3-b)indole; D007501:Iron; C007020:chlorophyllin