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Abstract

Metabolism of benzene in rat hepatocytes. Influence of inducers on phenol glucuronidation.

D Schrenk and K W Bock
Drug Metabolism and Disposition September 1990, 18 (5) 720-725;
D Schrenk
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Abstract

Alterations of benzene metabolism in liver markedly influence benzene toxicity at extrahepatic target tissues. Therefore, generation of 11 phase I and II metabolites of benzene (including phenol, hydroquinone, catechol, benzene-1,2-dihydrodiol, their sulfates and glucuronides, and phenylglutathione) was compared in hepatocytes from 3-methylcholanthrene (MC)- or phenobarbital-treated rats and from untreated controls. At 0.1 mM benzene, total metabolism appeared to be unchanged by treatment with inducers. Phenylsulfate (35%), phenylglucuronide (15%), and phenylglutathione (12%) represented the major metabolites in hepatocytes from untreated controls. With hepatocytes from MC-treated rats, a pronounced shift from phenylsulfate to phenylglucuronide (increase to 34%) was observed, while the formation of unconjugated phenol, hydroquinone, and catechol was decreased (from 16 to 10%). A similar shift from sulfation to glucuronidation was seen in similar studies with phenol. Lineweaver-Burk analysis of microsomal phenol UDP-glucuronosyltransferase activity suggested that MC-treatment induced a high affinity isozyme (KM = 0.14 mM), in addition to the low affinity isozyme (KM = 3.1 mM) present in liver microsomes from untreated and phenobarbital-treated rats. It is concluded that induction by MC of a high affinity hepatic phenol UDP-glucuronosyltransferase effectively shifts benzene metabolism toward formation of less toxic metabolites. This shift may reduce toxic risks at extrahepatic target tissues.

 

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Drug Metabolism and Disposition
Vol. 18, Issue 5
1 Sep 1990
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Abstract

Metabolism of benzene in rat hepatocytes. Influence of inducers on phenol glucuronidation.

D Schrenk and K W Bock
Drug Metabolism and Disposition September 1, 1990, 18 (5) 720-725;

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Abstract

Metabolism of benzene in rat hepatocytes. Influence of inducers on phenol glucuronidation.

D Schrenk and K W Bock
Drug Metabolism and Disposition September 1, 1990, 18 (5) 720-725;
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