Metabolic activation of hydroquinone by macrophage peroxidase.

Lysates from macrophages, cells involved in hematopoiesis and immunological responses, catalyzed the metabolic activation of the benzene metabolite, hydroquinone, to protein-binding compounds and to free 1,4-benzoquinone. This reaction is mediated by a peroxidase since activation was dependent upon H2O2 and was prevented by the inhibitors aminotriazole and azide. Activation of hydroquinone was independent of HO. radicals since protein binding occurred in the presence of the HO. scavengers mannitol and dimethyl sulfoxide. In reactions with macrophage lysates, phenol, another hepatic metabolite of benzene, stimulated the production of 1,4-benzoquinone as well as the amount of hydroquinone equivalents bound to protein in a dose-dependent manner. Addition of cysteine to incubations with macrophage lysates resulted in a dose-dependent decrease in hydroquinone equivalents bound to protein. At 100 microM cysteine, protein binding was inhibited by 63% and this decrease was recovered as the monocysteine-hydroquinone conjugate. Macrophages catalyzed the arachidonic acid-mediated activation of hydroquinone to metabolites which bound to cellular macromolecules. This activation was inhibited by indomethacin indicating the action of prostaglandin synthase in hydroquinone metabolism by macrophages. The results of these experiments demonstrate that macrophage peroxidase catalyzes the metabolic oxidation of hydroquinone to 1,4-benzoquinone and that 1,4-benzoquinone and/or its semiquinone intermediate are binding to protein and cysteine. Hydroquinone activation by macrophages and subsequent macromolecular binding may be associated with the immunologic and hematopoietic toxicity of benzene.