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

Abstract

1. Rats dosed with nitrosobenzene (56 μmol/kg), 4-chloronitrosobenzene (53 μmol/kg), 3,4-dichloronitrosobenzene (53 μmol/kg), 4-ethoxynitrosobenzene (86 μmol/kg), 4-nitrosobiphenyl(nitroso-BP, 55 μmol/kg) or 2-nitrosofluorcne (256 μmol/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.