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The metabolism of 4-aminobiphenyl in rat. IV. Ferrihaemoglobin formation by 4-aminobiphenyl metabolites

 

作者: KarrethS.,   LenkW.,  

 

期刊: Xenobiotica  (Taylor Available online 1991)
卷期: Volume 21, issue 7  

页码: 971-977

 

ISSN:0049-8254

 

年代: 1991

 

DOI:10.3109/00498259109039536

 

出版商: Taylor&Francis

 

数据来源: Taylor

 

摘要:

1. Rats dosed with nitrosobenzene (56μmol/kg), 4-chloronitrosobenzene (53μmol/kg), 3,4-dichloronitrosobenzene (53μmol/kg), 4-ethoxynitrosobenzene (86μmol/kg), 4-nitrosobiphenyl(nitroso-BP, 55μmol/kg) or 2-nitrosofluorcne (256μmol/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°C was k2= 19.1±1.31/mol per s.

 

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