Phase 11 Metabolism of Benzene Have to Be Identified
Phase 11 Metabolism of Benzene have to be identified. Application of single metabolites of benzene such as phenol Dieter Schrenk,1 Achim Orzechowski,1 (PH), catechol (CT), hydroquinone (HQ), and 1,2,4-trihydroxybenzene (THB) to Leslie R. Schwarz,2 Robert Snyder,3 Brian Burchell,4 rodents failed to reproduce the characteristic Magnus lngelman-Sundberg,5 and Karl Walter Bock1 toxic effects of benzene in the bone marrow (4,5). In several studies the possible syner- 1'nstitute of Toxicology, University of Tubingen, Tubingen, Germany; gistic action of certain metabolites of ben- 2GSF-lnstitute of Toxicology, Neuherberg/Munchen, Germany; zene on the bone marrow was investigated. 3Department of Pharmacology and Toxicology, EOHSI, Piscataway, It was shown that PH enhanced the conver- New Jersey; 4Department of Biochemical Medicine, University of sion of HQ into 1,4-benzoquinone cat- Dundee, Ninewells Hospital and Medical School, Dundee, United alyzed in vitro by myeloperoxidase (6,7), an Kingdom; 5Department of Physiological Chemistry, Karolinska Institute, enzyme present in abundance in the bone marrow (8). The electrophilic 1,4-benzo- Stockholm, Sweden quinone thus formed is able to bind to cel- The hepatic metabolism of benzene is thought to be a prerequisite for its bone marrow toxicity. lular proteins and DNA. Binding to critical However, the complete pattern of benzene metabolites formed in the liver and their role in bone proteins such as tubulin (9) or DNA poly- marrow toxicity are not fully understood. Therefore, benzene metabolism was studied in isolated merase-a (10) may play an important role rodent hepatocytes. Rat hepatocytes released benzene-1,2-dihydrodiol, hydroquinone (HQ), in benzene toxicity.
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