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-substit uted cysteinyl adducts of 1,4-benzoquinone (1,4-BQ) was investigated in bot h hemoglobin (Hb) and albumin (Alb) following administration of a single or al dose of 400 mg [U-C-14/ C-13(6)]benzene/kg body weight to F344 rats. Tot al radiobound adducts to Hb were stable, as were adducts formed by the reac tion of [C-13(6)]BO with cysteinyl residues on Hb. In both cases adduct sta bility was indicated by zero-order kinetics with decay rates consistent wit h 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 e rythrocyte. Regarding Alb binding, total radiobound adducts decayed more ra pidly than expected (half-life of 0.4 days), suggesting that uncharacterize d benzene metabolites were noncovalently bound or formed unstable adducts w ith Alb. Although adducts from reactions of BO and 1,4-BQ with Alb both dec ayed 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 adduc t instability in humans and rats, the 1,4-BQ-AIb adducts would be eliminate d with a half-life of approximately 8 days, compared with BO-Alb, which wou ld be expected to turnover with Alb (half-life of approximately 21 days).