Phase II metabolism of benzene
- Univ. of Tuebingen (Germany); and others
The hepatic metabolism of benzene is thought to be a prerequisite for its bone marrow toxicity. However, the complete pattern of benzene metabolites formed in the liver and their role in bone marrow toxicity are not fully understood. Therefore, benzene metabolism was studied in isolated rodent hepatocytes. Rat hepatocytes released benzene-1,2-dihydrodiol, hydroquinone (HQ), catechol (CT), phenol (PH), trans-trans-muconic acid, and a number of phase 11 metabolites such as PH sulfate and PH glucuronide. Pretreatment of animals with 3-methylcholanthrene (3-MC) markedly increased PH glucuronide formation while PH sulfate formation was decreased. Likewise, V79 cells transfected with the 3-MC-inducible rat UGT1.6 cDNA showed a considerable rate of PH and HQ glucuronidation. In addition to inducing glucuroniclation of phenols, 3-MC treatment (reported to protect rats from the myelotoxicity of benzene) resulted in a decrease of hepatic CYP2E1. In contrast, pretreatment of rats with the CYP2E1-inducer isopropanol strongly enhanced benzene metabolism and the formation of phenolic metabolites. Mouse hepatocytes formed much higher amounts of HQ than rat hepatocytes and considerable amounts of 1,2,4-trihydroxybenzene (THB) sulfate and HQ sulfate. In conclusion, the protective effect of 3-MC in rats is probably due to a shift from the labile PH sulfate to the more stable PH glucuronide, and to a decrease in hepatic CYP2E1. The higher susceptibility of mice toward benzene may be related to the high rate of formation of the myelotoxic metabolite HQ and the semistable phase 11 metabolites HQ sulfate and THB sulfate. 31 refs., 5 figs., 2 tabs.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 472158
- Report Number(s):
- CONF-9506288--
- Journal Information:
- Environmental Health Perspectives, Journal Name: Environmental Health Perspectives Journal Issue: Suppl.6 Vol. 104; ISSN EVHPAZ; ISSN 0091-6765
- Country of Publication:
- United States
- Language:
- English
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