The hydroxylation, dechlorination, and glucuronidation of 4,4'-dichlorobiphenyl (4-DCB) by human hepatic microsomes.


:Since chlorine placement and the degree of chlorination of the biphenyl nucleus play an important role in the metabolism and ultimate elimination of polychlorinated biphenyls (PCBs), we have studied the metabolism of 4,4'-dichlorobiphenyl (4-DCB) by human hepatic microsomes. This low molecular weight PCB congener is substituted at the preferred site of metabolism (para-position). 4-DCB was metabolized by human microsomes with a Km of 0.43 microM and a Vmax of 1.2 pmoles/mg microsomal protein/min. Six metabolites were identified: 4,4'-dichloro-3,3'-biphenyldiol, 4'-chloro-3-biphenylol, 4'-chloro-4-biphenylol, 4,4'-dichloro-2-biphenylol, 4,4'-dichloro-3-biphenylol (most abundant), and 3,4'-dichloro-4-biphenylol. [14C]-4-DCB equivalents were found to covalently bind to microsomal protein. Addition of a 1 mM concentration of reduced glutathione decreased the degree of covalent binding. These data suggest that human microsomes metabolize this PCB through an arene oxide and that an "NIH shift" occurs. When UDPGA was added to the incubation, human microsomal glucuronosyltransferase catalyzed the formation of the glucuronide of the major metabolite, 4,4'-dichloro-3-biphenylol. These and previous in vitro results show that the biotransformation of PCBs by humans is governed by the same principles established for the in vivo biotransformation of PCBs by the rat, mouse and monkey. That is, PCBs without two adjacent unsubstituted carbon atoms are poorly metabolized and that an unsubstituted para-position facilitates metabolism.


Biochem Pharmacol


Biochemical pharmacology


Schnellmann RG,Volp RF,Putnam CW,Sipes IG




Has Abstract


1984-11-01 00:00:00














  • CagA protein of Helicobacter pylori: a hijacker of gastric epithelial cell signaling.

    abstract::Epidemiological study has shown strong correlation between the Helicobacter pylori (H. pylori) infection and gastric carcinogenesis. However, the mechanism by which H. pylori induces gastric carcinogenesis is not known. In this review, we focused on the product of cytotoxin-associated gene A (CagA), one of the importa...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Handa O,Naito Y,Yoshikawa T

    更新日期:2007-06-01 00:00:00

  • Transforming growth factor-beta3 protection of epithelial cells from cycle-selective chemotherapy in vitro.

    abstract::The transforming growth factor-beta (TGF-beta) family of regulatory growth factors can reversibly arrest cell division in the G1 phase of the cell cycle. Previously, TGF-beta3 was shown to protect epithelial cells and hematopoietic cells from cytotoxic damage in vitro and in vivo, and to reduce the severity and durati...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: McCormack ES,Borzillo GV,Ambrosino C,Mak G,Hamablet L,Qu GY,Haley JD

    更新日期:1997-04-25 00:00:00

  • Cerium-induced strain-dependent increase in Cyp2a-4/5 (cytochrome P4502a-4/5) expression in the liver and kidneys of inbred mice.

    abstract::The murine Cyp2a-4 and Cyp2a-5 genes encode P450 isoforms catalysing testosterone 15 alpha-hydroxylase and coumarin 7-hydroxylase (COH) activities, respectively. Two days after the administration of a hepatotoxic dose of cerium chloride (2 mg/kg i.v.), COH activity was increased 3.2-fold in the liver of DBA/2 mice. Th...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Salonpää P,Iscan M,Pasanen M,Arvela P,Pelkonen O,Raunio H

    更新日期:1992-10-06 00:00:00

  • DNA-DNA interstrand crosslinking by dimethyanesulphonic acid esters. Correlation with cytotoxicity and antitumour activity in the Yoshida lymphosarcoma model and relationship to chain length.

    abstract::Members of the homologous series of nine antitumour dimethanesulphonic acid esters, with the exception of ethylene dimethanesulphonate (EDMS), were found to cause DNA-DNA interstrand crosslinking in cells derived from the transplantable rodent Yoshida lymphosarcoma. The ability of the series to induce interstrand cros...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Bedford P,Fox BW

    更新日期:1983-08-01 00:00:00

  • Differential inhibition of cellular glutathione reductase activity by isocyanates generated from the antitumor prodrugs Cloretazine and BCNU.

    abstract::The antitumor, DNA-alkylating agent 1,3-bis[2-chloroethyl]-2-nitrosourea (BCNU; Carmustine), which generates 2-chloroethyl isocyanate upon decomposition in situ, inhibits cellular glutathione reductase (GR; EC activity by up to 90% at pharmacological doses. GR is susceptible to attack from exogenous electroph...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Rice KP,Penketh PG,Shyam K,Sartorelli AC

    更新日期:2005-05-15 00:00:00

  • Increased concentrations of methylated 6-mercaptopurine metabolites and 6-thioguanine nucleotides in human leukemic cells in vitro by methotrexate.

    abstract::The effect of methotrexate (MTX) on 6-mercaptopurine (6-MP) metabolism was studied in four human leukemic cell lines in vitro. CCRF-CEM, WI-L2, TBJ, and HL-60 all expressed thiopurine methyltransferase (TPMT) activity. The cells were grown in horse serum-supplemented RPMI 1640 medium to which was added 4 microM of 6-M...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Giverhaug T,Loennechen T,Aarbakke J

    更新日期:1998-05-15 00:00:00

  • Telatinib reverses chemotherapeutic multidrug resistance mediated by ABCG2 efflux transporter in vitro and in vivo.

    abstract::Multidrug resistance (MDR) is a phenomenon where cancer cells become simultaneously resistant to anticancer drugs with different structures and mechanisms of action. MDR has been shown to be associated with overexpression of ATP-binding cassette (ABC) transporters. Here, we report that telatinib, a small molecule tyro...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Sodani K,Patel A,Anreddy N,Singh S,Yang DH,Kathawala RJ,Kumar P,Talele TT,Chen ZS

    更新日期:2014-05-01 00:00:00

  • Structure-activity relationship of pyrimidine base analogs as ligands of orotate phosphoribosyltransferase.

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Niedzwicki JG,Iltzsch MH,el Kouni MH,Cha S

    更新日期:1984-08-01 00:00:00

  • Pharmacological characterisation of the plant sesquiterpenes polygodial and drimanial as vanilloid receptor agonists.

    abstract::This study was designed to assess the participation of transient receptor potential vanilloid 1 (TRPV1) in the biological effects induced by the plant-derived sesquiterpenes polygodial and drimanial. In rat isolated urinary bladder, polygodial and drimanial produced a tachykinin-mediated contraction that was inhibited...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: André E,Campi B,Trevisani M,Ferreira J,Malheiros A,Yunes RA,Calixto JB,Geppetti P

    更新日期:2006-04-14 00:00:00

  • Regulation on SIRT1-PGC-1α/Nrf2 pathway together with selective inhibition of aldose reductase makes compound hr5F a potential agent for the treatment of diabetic complications.

    abstract::(R,E)-N-(3-(2-acetamido-3-(benzyloxy) propanamido)propyl)-2-cyano-3-(4-hydroxy phenyl)acrylamide (hr5F) was design-synthesized based on bioactivity focus strategy as a potential agent to treat diabetic complicates. With in vitro enzyme assay, it is confirmed that hr5F is an effective ALR2 inhibitor with IC50 value of ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Wang Z,Yuan S,Li Y,Zhang Z,Xiao W,Tang D,Ye K,Liu Z,Wang C,Zheng Y,Nie H,Chen H

    更新日期:2018-04-01 00:00:00

  • Suppression of cytokine production and neural cell death by the anti-inflammatory alkaloid cepharanthine: a potential agent against HIV-1 encephalopathy.

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Okamoto M,Ono M,Baba M

    更新日期:2001-09-15 00:00:00

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Padiglia A,Medda R,Lorrai A,Biggio G,Sanna E,Floris G

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  • Phenylhydrazine-induced lipid peroxidation of red blood cells in vitro and in vivo: monitoring by the production of volatile hydrocarbons.

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Clemens MR,Remmer H,Waller HD

    更新日期:1984-06-01 00:00:00

  • Beneficial effects of L-carnitine in myoblastic C2C12 cells. Interaction with zidovudine.

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    pub_type: 杂志文章


    authors: Georges B,Galland S,Rigault C,Le Borgne F,Demarquoy J

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    pub_type: 杂志文章


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  • Pharmacogenetics of human 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 (PAPSS1): gene resequencing, sequence variation, and functional genomics.

    abstract::3'-Phosphoadenosine 5'-phosphosulfate (PAPS) is the high-energy "sulfate donor" for reactions catalyzed by sulfotransferase (SULT) enzymes. The strict requirement of SULTs for PAPS suggests that PAPS synthesis might influence the rate of sulfate conjugation. In humans, PAPS is synthesized from ATP and SO(4)(2-) by two...

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    authors: Xu ZH,Thomae BA,Eckloff BW,Wieben ED,Weinshilboum RM

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  • The toxicological relevance of paracetamol-induced inhibition of hepatic respiration and ATP depletion.

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    authors: Strubelt O,Younes M

    更新日期:1992-07-07 00:00:00

  • A direct link between LY83583, a selective repressor of cyclic GMP formation, and glutathione metabolism.

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    authors: Lüönd RM,McKie JH,Douglas KT

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Lindsay RM,Baird JD

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  • New insights into generalized hepatoprotective effects of oleanolic acid: key roles of metallothionein and Nrf2 induction.

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Liu J,Wu Q,Lu YF,Pi J

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Toth A,Kovacs K,Deres P,Halmosi R,Czopf L,Hanto K,Kalai T,Hideg K,Sumegi B,Toth K

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Ng DS,Isom GE

    更新日期:1985-08-15 00:00:00

  • Cisplatin-induced apoptosis by translocation of endogenous Bax in mouse collecting duct cells.

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Lee RH,Song JM,Park MY,Kang SK,Kim YK,Jung JS

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Vinci MC,Visentin B,Cusinato F,Nardelli GB,Trevisi L,Luciani S

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Zilberman Y,Gutman Y

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Qiao L,Hanif R,Sphicas E,Shiff SJ,Rigas B

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Furihata T,Hosokawa M,Fujii A,Derbel M,Satoh T,Chiba K

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Adachi T,Fukuta M,Ito Y,Hirano K,Sugiura M,Sugiura K

    更新日期:1986-01-15 00:00:00

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Brodsky JL

    更新日期:1999-04-15 00:00:00