Stability of hemoglobin and albumin adducts of benzene oxide and 1,4-benzoquinone after administration of benzene to F344 rats.

The stability of cysteinyl adducts of benzene oxide (BO) and mono-S-substituted cysteinyl adducts of 1,4-benzoquinone (1,4-BQ) was investigated in both hemoglobin (Hb) and albumin (Alb) following administration of a single oral dose of 400 mg [U-14C/13C6]benzene/kg body weight to F344 rats. Total radiobound adducts to Hb were stable, as were adducts formed by the reaction of [13C6]BO with cysteinyl residues on Hb. In both cases adduct stability was indicated by zero-order kinetics with decay rates consistent with the lifetime of rat erythrocytes. Hb adducts of 1,4-BQ were not detected, possibly due to the production of multi-S-substituted adducts within the erythrocyte. Regarding Alb binding, total radiobound adducts decayed more rapidly than expected (half-life of 0.4 days), suggesting that uncharacterized benzene metabolites were noncovalently bound or formed unstable adducts with Alb. Although adducts from reactions of BO and 1,4-BQ with Alb both decayed with rates consistent with those of Alb turnover in the rat, the half-life for 1,4-BQ-Alb (2.5 days) was shorter than that for BO-Alb (3.1 days), suggesting some instability of 1,4-BQ-Alb. Assuming similar rates of adduct instability in humans and rats, the 1,4-BQ-Alb adducts would be eliminated with a half-life of approximately 8 days, compared with BO-Alb, which would be expected to turnover with Alb (half-life of approximately 21 days).