Benzene: a case study in parent chemical and metabolite interactions.


:Benzene, an important industrial solvent, is also present in unleaded gasoline and cigarette smoke. The hematotoxic effects of benzene in humans are well documented and include aplastic anemia and pancytopenia, and acute myelogenous leukemia. A combination of metabolites (hydroquinone and phenol for example) is apparently necessary to duplicate the hematotoxic effect of benzene, perhaps due in part to the synergistic effect of phenol on myeloperoxidase-mediated oxidation of hydroquinone to the reactive metabolite benzoquinone. Since benzene and its hydroxylated metabolites (phenol, hydroquinone and catechol) are substrates for the same cytochrome P450 enzymes, competitive interactions among the metabolites are possible. In vivo data on metabolite formation by mice exposed to various benzene concentrations are consistent with competitive inhibition of phenol oxidation by benzene. In vitro studies of the metabolic oxidation of benzene, phenol and hydroquinone are consistent with the mechanism of competitive interaction among the metabolites. The dosimetry of benzene and its metabolites in the target tissue, bone marrow, depends on the balance of activation processes such as enzymatic oxidation and deactivation processes such as conjugation and excretion. Phenol, the primary benzene metabolite, can undergo both oxidation and conjugation. Thus, the potential exists for competition among various enzymes for phenol. However, zonal localization of Phase I and Phase II enzymes in various regions of the liver acinus regulates this competition. Biologically-based dosimetry models that incorporate the important determinants of benzene flux, including interactions with other chemicals, will enable prediction of target tissue doses of benzene and metabolites at low exposure concentrations relevant for humans.






Medinsky MA,Kenyon EM,Schlosser PM




Has Abstract


1995-12-28 00:00:00














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    authors: Agarwal AK,Mehendale HM

    更新日期:1984-02-01 00:00:00

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    authors: Attia SM

    更新日期:2007-06-03 00:00:00

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    authors: Chauhan SS,Singh SK,Misra UK

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    pub_type: 杂志文章


    authors: Miura K,Goldstein RS,Pasino DA,Hook JB

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    authors: Forkert PG,Sylvestre PL,Poland JS

    更新日期:1985-05-01 00:00:00

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    authors: Vidal L,Durán R,Faro LF,Campos F,Cervantes RC,Alfonso M

    更新日期:2007-09-05 00:00:00

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    pub_type: 杂志文章


    authors: Gorman D,Lin HY,Williams C

    更新日期:2005-05-05 00:00:00

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    authors: Balletta A,Lorenz D,Rummel A,Gerhard R,Bigalke H,Wegner F

    更新日期:2015-02-03 00:00:00

  • Hepatic fibrosis -- overview.

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    pub_type: 杂志文章,评审


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    更新日期:2008-12-30 00:00:00

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    authors: Hochadel JF,Waalkes MP

    更新日期:1997-01-15 00:00:00

  • Porcine hepatocyte apoptosis and reduction of albumin secretion induced by deoxynivalenol.

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    authors: Mikami O,Yamamoto S,Yamanaka N,Nakajima Y

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    authors: Raha A,Reddy V,Xu LC,Houser WH,Bresnick E

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    authors: Moto M,Okamura M,Muto T,Kashida Y,Machida N,Mistumori K

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    authors: Ardelt BK,Borowitz JL,Maduh EU,Swain SL,Isom GE

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    pub_type: 杂志文章


    authors: Lehmann T,Köhler C,Weidauer E,Taege C,Foth H

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    pub_type: 杂志文章


    authors: Lisciani R,Baldini A,Benedetti D,Campana A,Barcellona PS

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    pub_type: 杂志文章


    authors: Johansson L

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    pub_type: 杂志文章


    authors: Muliawan H,Kappus H

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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    pub_type: 杂志文章


    authors: Oskarsson A,Johansson A

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