Detoxication of N-oxygenated arylamines in erythrocytes. An overview.

1. Reactive N-oxygenated arylamines, namely, N-hydroxyarylamines and nitrosoarenes, are toxic, mutagenic, carcinogenic and allergenic. 2. Erythrocytes are a very sensitive target for these compounds, but little is known of the detoxication capacity of these cells. 3. This overview considers the most important reactions of p-substituted N-oxygenated arylamines in red cells, namely, (i) ferrihaemoglobin formation by N-hydroxyarylamines with concomitant co-oxidation to nitrosoarenes; (ii) compartmentation of nitrosobenzenes by ligation to deoxyhaemoglobin, (iii) reactions of nitrosobenzene with glutathione, (iv) adduct formation of nitrosobenzenes with thiol groups of haemoglobin. 4. To predict the metabolic fate of N-oxygenated arylamines in red cells, the respective kinetic parameters of reactions (i) to (iv) have been determined, and indicate good linear free energy correlations (pH 7.4, 37 degrees C). These data may help to estimate the detoxication capacity of erythrocytes in vivo.