The mutagenic modulating effect of p-phenylenediamine on the oxidation of o- or m-phenylenediamine with hydrogen peroxide in the Salmonella test.
The mutagenicity of o- and m-phenylenediamine (PD) was remarkedly enhanced by oxidation; their major mutagenic oxidation products were 2,3- and 2,7-diaminophenazine, respectively. In order to evaluate the modulation effect of p-PD on the oxidation of m- or o-PD, p-PD and mixtures of m- and p-PD (m-PD/p-PD) and o- and p-PD (o-PD/p-PD) were oxidized with hydrogen peroxide and their mutagenicity was tested in Salmonella typhimurium TA98 in the presence or absence of a mammalian metabolic activation system (S9 mix). The H2O2-oxidized m-PD/p-PD and o-PD/p-PD were potent mutagens with S9 mix, whereas H2O2-oxidized p-PD was slightly mutagenic. The major mutagenic oxidation products of m-PD/p-PD and o-PD/p-PD were identified as 2,7- and 2,3-diaminophenazine, respectively, by TLC and HPLC. 2,8-Diaminophenazine was also found as a reaction product in oxidized m-PD/p-PD, and it was weakly mutagenic. The mutagenic potency of oxidized m-PD/p-PD or o-PD/p-PD was lower than that of singly oxidized m-PD or o-PD. The yield of 2,7- and 2,3-diaminophenazine was obviously decreased with increases in p-PD, and it was concluded that the declined mutagenic potency of oxidized m-PD/p-PD or o-PD/p-PD was due to the decrease in diaminophenazines. But the formation of diaminophenazines was not completely inhibited by the addition of a 9-fold molar ratio of p-PD to m-PD or o-PD, 8.6 nmole of 2,7-diaminophenazine and 1882.4 nmole of 2,3-diaminophenazine were formed from 1 mmole of m-PD and o-PD, respectively.
Kyoto Pharmaceutical University, Japan.
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Watanabe
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Hirayama
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Fukui
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004357:Drug Synergism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D010084:Oxidation-Reduction; D010619:Phenazines / Q000032:analysis; D010655:Phenylenediamines / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects
D010619:Phenazines; D010655:Phenylenediamines; C054312:2,3-diaminophenazine; C065504:2,7-diaminophenazine; C034193:1,2-diaminobenzene; D006861:Hydrogen Peroxide; C008381:3-phenylenediamine; C029728:4-phenylenediamine