The metabolism of 4-aminobiphenyl in rat. IV. Ferrihaemoglobin formation by 4-aminobiphenyl metabolites.
1. Rats dosed with nitrosobenzene (56 mumol/kg), 4-chloronitrosobenzene (53 mumol/kg), 3,4-dichloronitrosobenzene (53 mumol/kg), 4-ethoxynitrosobenzene (86 mumol/kg), 4-nitrosobiphenyl(nitroso-BP, 55 mumol/kg) or 2-nitrosofluorene (256 mumol/kg) had maximal ferrihaemoglobin (HbFe3+) concn of 69, 68, 69, 67, 55 and 42% after 15, 25, 48, 35, 80 and 115 min, respectively, indicating differences in solubility of the nitrosoarenes in body fluids. 2. Nitroso-BP and 3-hydroxy-4-aminobiphenyl (3-hydroxy-ABP) catalytically oxidized HbFe2+ in bovine erythrocytes in vitro; nitroso-BP was three times as active as 3-hydroxy-ABP. 3',4'-Dihydroxy-4-aminobiphenyl (3',4'dihydroxy-ABP) showed only low catalytic activity, and seven other ABP metabolites exhibited only marginal activity. 3. Nitroso-BP was inactive in solutions of purified human Hb, but 3-hydroxy-ABP catalytically oxidized HbFe2+, indicating that nitrosoarenes oxidize HbFe2+ in erythrocytes in vitro and in vivo by a mechanism different from that of o-aminophenols. The second-order rate constant for HbFe2+ oxidation by 3-hydroxy-ABP at 37 degrees C was k2 = 19.1 +/- 1.31/mol per s.
Karreth
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S
Walther Straub-Institut für Pharmakologie und Toxikologie, LM-Universität München, Germany.
Lenk
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W
D000611:Aminobiphenyl Compounds / Q000378:metabolism*; D000818:Animals; D002384:Catalysis; D002417:Cattle; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D008196:Lymph / Q000378:metabolism; D008706:Methemoglobin / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D000611:Aminobiphenyl Compounds; C006757:4-biphenylamine; C014593:N-hydroxy-4-aminobiphenyl; D008706:Methemoglobin