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.
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 significantly. The presence of excess hemin with N-hydroxy-Trp-P-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/Trp-P-2. In support of this view, the fluorescence spectrum of a Trp-P-2 solution was quenched efficiently 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.
Arimoto
S
S
Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Hayatsu
H
H
D001711:Biotransformation; D002243:Carbolines / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D006418:Heme / Q000031:analogs & derivatives*; D006427:Hemin / Q000494:pharmacology*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000493:pharmacokinetics; D012486:Salmonella typhimurium / Q000235:genetics; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet
D002243:Carbolines; D009153:Mutagens; D006418:Heme; D006427:Hemin; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole