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J.Health Sci., 55(1), 109-113, 2009
Effect of Substituted Aryl Group in Water-soluble Porphyrins on 2-Aminofluorene Activation in Ames Assay
Keiko Inami,*, a, b Akiko Inokawa,a
Yayoi Sugita,a and Masataka Mochizukia, b
aKyoritsu University of Pharmacy, Shibakoen 1530, Minato-ku, Tokyo 1058512, Japan and
bFaculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 2788510, Japan
Chemical models for cytochrome P450, consisting of an iron porphyrin complex and an oxidant, have been used as substitutes for the S-9 mix for detecting mutagenicity of promutagens in the Ames assay. In this study, we developed optimized procedures for the Ames mutation assay using a water-insoluble 5,10,15,20-tetrakis(pentafluorophenyl)porphyrinatoiron(III) chloride (F5P) or a water-soluble 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrinatoiron(III) (4-MPy) plus tert-butyl hydroperoxide (t-BuOOH) as a chemical model to determine 2-aminofluorene (AF) mutagenicity. The model system including the water-insoluble F5P plus t-BuOOH demonstrated higher AF mutagenicity when the tester strain was added following the incubation period of the reaction mixture. In contrast, in the system including the water-soluble 4-MPy plus t-BuOOH, the activity of AF mutagenicity was highest when the tester strain was added to the reaction mixture prior to incubation. It is thus possible to detect short-lived mutagenic metabolites by the latter procedure. AF mutagenicity was compared among diverse water-soluble iron porphyrins plus t-BuOOH. The results showed that a cationic 4-MPy/t-BuOOH had the highest capacity for mutagenic activation of AF among the chemical models tested.
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