Comparison of protein adducts of benzene oxide and benzoquinone in the blood and bone marrow of rats and mice exposed to [14C/13C6]benzene.

Protein binding of hemoglobin (Hb) and bone marrow was used to compare in vivo reactions of 3 electrophilic metabolites of benzene, i.e., benzene oxide and 1,2- and 1,4-benzoquinone (1, 2-BQ and 1, 4-BQ), in F344 rats and B6C3F1 mice. Following a single p.o. administration of a mixture of [14C]- and [13C6]benzene between 50 and 400 mg/kg body weight, cysteine adducts of benzene oxide, 1,2-BQ, and 1,4-BQ were assayed, and the proportions of cysteine-bound adducts to total protein binding were estimated. Although dose-related production of each adduct was seen, large differences were observed between species and tissues. With rat Hb, benzene oxide adducts represented 27% of the total Hb binding and 73% of the cysteinyl binding, whereas quinone adducts represented relatively small proportions. However, with mouse Hb, the 1,4-BQ adducts accounted for 5.5% of the total Hb binding and 12.2% of the cysteinyl binding, while 1,2-BQ and benzene oxide each accounted for less than 3% of the total. In the bone marrow of both rats and mice, BQ adducts were more abundant than those of benzene oxide. However, adducts of 1,2-BQ predominated in rat marrow (9% of binding), whereas adducts of 1,4-BQ were more abundant in the mouse (21% of binding). The average blood concentrations of 1,4-BQ were estimated from the adduct levels and reaction-rate constants to be 2-5-fold higher in the mouse than in the rat. This work suggests that BQ binding is favored over that of benzene oxide in the bone marrow; however, high background levels of BQ adducts, observed with Hb and bone marrow proteins, suggest that any toxic effects of the quinones should only arise from high exposures to benzene.