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Titolo:
PHASE-II METABOLISM OF BENZENE
Autore:
SCHRENK D; ORZECHOWSKI A; SCHWARZ LR; SNYDER R; BURCHELL B; INGELMANSUNDBERG M; BOCK KW;
Indirizzi:
UNIV TUBINGEN,INST TOXICOL,WILHELMSTR 56 D-72074 TUBINGEN GERMANY GSF MUNICH,INST TOXICOL MUNICH GERMANY EOHSI,DEPT PHARMACOL & TOXICOL PISCATAWAY NJ 00000 UNIV DUNDEE,NINEWELLS HOSP & MED SCH,DEPT BIOCHEM MED DUNDEE DD1 9SY SCOTLAND KAROLINSKA INST,DEPT PHYSIOL CHEM S-10401 STOCKHOLM SWEDEN
Titolo Testata:
Environmental health perspectives
, volume: 104, anno: 1996, supplemento:, 6
pagine: 1183 - 1188
SICI:
0091-6765(1996)104:<1183:PMOB>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT HEPATOCYTES; TOXICITY; HYDROQUINONE; ETHANOL; LIVER; MICE; CARCINOGENICITY; DISPOSITION; MICROSOMES; INDUCTION;
Keywords:
BENZENE METABOLISM; CYTOCHROME P4502E1; DRUG-METABOLIZING ENZYMES; GLUCURONIDATION; HEPATOCYTES; HYDROQUINONE FORMATION; INDUCERS OF DRUG METABOLISM; SULFATE CONJUGATES; UDP-GLUCURONOSYLTRANSFERASE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
31
Recensione:
Indirizzi per estratti:
Citazione:
D. Schrenk et al., "PHASE-II METABOLISM OF BENZENE", Environmental health perspectives, 104, 1996, pp. 1183-1188

Abstract

The hepatic metabolism of benzene is thought to be a prerequisite forits 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 II 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 glucuronidation 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 II metabolites HQ sulfate and THE sulfate.

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Documento generato il 22/09/20 alle ore 10:06:34