Evidence for common binding of acetaminophen and bromobenzene to the 58‐kda acetaminophen‐binding protein

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Abstract
Acetaminophen (APAP) toxicity has been closely associated with covalent binding to a cytosolic protein of approximately 58 kDa (58‐ABP). To determine if metabolites of other toxicants might also selectively target this protein, studies were conducted with bromobenzene (BrB). Mice were given phenobarbital (80 mg/kg/d × 4 d) and were killed 4 h after challenge with 800 mg BrB/kg. Liver cytosols from BrB‐treated or naive mice were incubated with an APAP activating system. Cytosolic fractions were analyzed for APAP binding by Western blotting with anti‐APAP antibody. Binding to 58‐ABP was selectively decreased in liver cytosol from BrB‐treated mice while binding to other targets was minimally affected. Western blotting of the same samples with anti‐58‐ABP antisera showed that this decrease in binding did not result from diminished 58‐ABP content. HPLC analysis of APAP‐N‐acetyl cysteine conjugate formation in vitro indicates that APAP activation was not altered in the incubates with cytosol from BrB‐treated mice. These results suggest that the 58‐ABP may be a common target for electrophiles in reactive intermediate toxicity.