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Bessems, J.G.M. (author), de Groot, M.J. (author), Baede, E.J. (author), te Koppele, J.M. (author), Vermeulen, N.P.E. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)1. The formation of free radicals during enzyme catalysed oxidation of eight 3,5-disubstituted analogues of paracetamol (PAR) has been studied. A simple peroxidase system as well as cytochrome P450-containing systems were used. Radicals were detected by electron spin resonance (ESR) on incubation of PAR and 3,5-diCH3-, 3,5-diC2H5-, 3,5-ditC4H9-,...article 1998
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Monshouwer, M. (author), van 't Klooster, G.A.E. (author), Nijmeijer, S.M. (author), Witkamp, R.F. (author), van Miert, A.S.J.P.A.M. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)Despite the fact that pigs are increasingly used in pharmacological and toxicological studies, knowledge on the enzymes which metabolize xenobiotics, in particular cytochrome P450 (CYP) enzymes, in pigs is still very limited. Primary cultures of pig hepatocytes were used to characterize CYP enzymes. The characterization was performed at the...article 1998
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van den Brink, H.M. (author), van Gorcom, R.F.M. (author), van den Hondel, C.A.M.J.J. (author), Punt, P.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)The involvement of cytochrome P450 enzymes in many complex fungal bioconversion processes has been characterized in recent years. Accordingly, there is now considerable scientific interest in fungal cytochrome P450 enzyme systems. In contrast to S. cerevisiae, where surprisingly few P450 genes have been identified, biochemical data suggest that...article 1998
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- de Groene, E.M. (author), Centraal Instituut voor Voedingsonderzoek TNO (author) article 1998
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Sherratt, P.J. (author), Manson, M.M. (author), Thomson, A.M. (author), Hissink, E.A.M. (author), Neal, G.E. (author), van Bladeren, P.J. (author), Green, T. (author), Hayes, J.D. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)A characteristic feature of the class Theta glutathione S-transferase (GST) T1-1 is its ability to activate dichloromethane and dibromoethane by catalysing the formation of mutagenic conjugates. The level of the GSTT1 subunit within tissues is an important determinant of susceptibility to the carcinogenic effects of these dihaloalkanes. In the...article 1998
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Dahl, M.L. (author), Voortman, G. (author), Alm, C. (author), Elwin, C.E. (author), Delbressine, L. (author), Vos, R. (author), Bogaards, J.J.P. (author), Bertilsson, L. (author), Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding (author)The novel antidepressant mirtazapine is a racemate with both noradrenergic and serotonergic potentiating effects. In vitro metabolism of racemic mirtazapine was studied in (a) microsomes from cells expressing different cytochrome P450 (CYP) enzymes and (b) human liver microsomes from 10 subjects and compared with the rate of metabolism of 4...article 1997
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TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO (author), Ploemen, J.P.H.T.M. (author), Wormhoudt, L.W. (author), Haenen, G.R.M.M. (author), Oudshoorn, M.J. (author), Commandeur, J.N.M. (author), Vermeulen, N.P.E. (author), de Waziers, I. (author), Beaune, P.H. (author), Watabe, T. (author), van Bladeren, P.J. (author)Ethylene dibromide (1,2-dibromoethane, EDB) is metabolized by two routes: a conjugative route catalyzed by glutathione S-transferases (GST) and an oxidative route catalyzed by cytochrome P450 (P450). The GST route is associated with carcinogenicity. An approach is presented to use human purified GST and P450 enzymes to explore the importance of...article 1997
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TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO (author), Hissink, A.M. (author), Oudshoorn, M.J. (author), van Ommen, B. (author), van Bladeren, P.J. (author)Our goal was to characterize possible species and strain differences in the hepatic microsomal biotransformation of 1,4-dichlorobenzene (1,4-DCB). Experiments compared extent of labeled 1,4-DCB conversion to oxidized metabolites, glutathione conjugates, and covalently bound metabolites by hepatic microsomes from humans, from male B6C3F1 mice,...article 1997
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Kappers, W.A. (author), de Groene, E.M. (author), Kleij, L.A. (author), Witkamp, R.F. (author), Zweers-Zeilmaker, W.M. (author), Feron, V.J. (author), Horbach, G.J. (author), TNO Voeding (author)1. To study the role of cytochrome P4502C10 in the metabolism of the non-steroidal antiinflammatory drugs (NSAIDs) diclofenac, phenylbutazone, fenoprofen, ibuprofen, flurbiprofen, ketoprofen and naproxen, a cell line was developed stably expressing CYP2C10 cDNA. A retroviral vector construct, containing a human CYP2C10 cDNA, was transfected in...article 1996
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Bessems, J.G.M. (author), te Koppele, J.M. (author), van Dijk, P.A. (author), van Stee, L.L.P. (author), Commandeur, J.N.M. (author), Vermeulen, N.P.E. (author), Leiden/Amsterdam Ctr. for Drug Res., Division of Molecular Toxicology, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, Netherlands Dept. Vasc. Connective Tissue Res TNO Preventie en Gezondheid (author)1. The cytochrome P450-dependent binding of paracetamol and a series of 3,5-disubstituted paracetamol analogues (R = -F, -Cl, -Br, -I, -C(H)3, -C2H5, -iC3H7) have been determined with β-naphthoflavone (βNF)-induced rat liver microsomes and produced reverse type I spectral changes. K(s,app) varied from 0.14 mM for 3,5-diiC3H7-paracetamol to 2.8...article 1996
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Hissink, A.M. (author), Oudshoorn, M.J. (author), van Ommen, B. (author), Haenen, G.R.M.M. (author), van Bladeren, P.J. (author)The oxidative biotransformation of 1, 2-dichlorobenzene (1, 2-DCB) was investigated using hepatic microsomes from male Wistar, Fischer-344 and Sprague-Dawley (SD) rats, phenobarbital (PB)- and isoniazid (ISO) pretreated male Wistar rats and from man. In addition, microsomes from cell lines selectively expressing one cytochrome P450 (P4502E1, 1A1...article 1996
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van den Brink, H.J.M. (author), van Nistelrooy, H.J.G.M. (author), de Waard, M.A. (author), van den Hondel, C.A.M.J.J. (author), van Gorcom, R.F.M. (author), Prins Maurits Laboratorium TNO (author)In this paper we describe the effects of over-expression of the Penicillium italicum gene encoding eburicol 14α-demethylase (cyp51), in Aspergillus niger strains with one or multiple copies of the gene encoding cytochrome P450 reductase (cpr A), on the eburicol 14α-demethylase activity. Eburicol 14α-demethylase activity was determined by...article 1996
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van Nistelrooy, J.G.M. (author), van den Brink, J.M. (author), van Kan, J.A.L. (author), van Gorcom, R.F.M. (author), de Waard, M.A. (author), Prins Maurits Laboratorium TNO (author)The CYP51 gene encoding eburicol 14α-demethylase (P450(14DM)) was cloned from a genomic library of the filamentous fungal plant pathogen Penicillium italicum, by heterologous hybridisation with the corresponding gene encoding lanosterol 14α-demethylase from the yeast Candida tropicalis. The nucleotide sequence of a 1739-bp genomic fragment and...article 1996
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Lansink, M. (author), Blaner, W.S. (author), Kooistra, T. (author), Gaubius Instituut TNO (author)Chemicals/CAS: cytochrome P450, 9035-51-2; retinoic acid, 302-79-4article 1996
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Bogaards, J.J.P. (author), Venekamp, J.C. (author), van Bladeren, P.J. (author)The metabolism of isoprene was investigated with microsomes derived from cell lines expressing human CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1, or CYP3A4. The formation of epoxide metabolites was determined by gas chromatographic analysis. CYP2E1 showed the highest rates of formation of the isoprene monoepoxides 3,4-epoxy-3-methyl-1...article 1996
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- Hissink, E. (author), van Ommen, B. (author), Bogaards, J.J. (author), van Bladeren, P.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author) article 1996
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Instituut CIVO-Toxicologie en Voeding TNO (author), den Besten, C. (author), van Bladeren, P.J. (author), Duizer, E. (author), Vervoort, J. (author), Rietjens, I.M.C.M. (author)In the present study the oxidative dehalogenation of a para-halogenated phenol was studied using pentafluorophenol and its non-para-halogenated analogue 2,3,5,6-tetrafluorophenol as model compounds. 19F NMR was used to characterize the metabolite patterns. In order to study the primary oxidation products of the microsomal cytochrome P450...article 1993
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Instituut CIVO-Toxicologie en Voeding TNO (author), Boyd, D.R. (author), Sharma, N.D. (author), Agarwal, R. (author), McMordie, R.A.S. (author), Bessems, J.G.M. (author), van Ommen, B. (author), van Bladeren, P.J. (author)Both 1,2-dihydronaphthalene and 1,2-dihydroanthracene were hydroxylated at the benzylic (1-) or the allylic (2-) position by rat liver microsomes and purified cytochrome P-450 enzymes to yield "arene hydrates". Two other classes of metabolites were formed, the dehydrogenation products naphthalene and anthracene, and trans-1,2-dihydroxy-1,2,3,4...article 1993
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Instituut voor Toxicologie en Voeding TNO (author), Wortelboer, H.M. (author), de Kruif, C.A. (author), van Iersela, A.A.J. (author), Falke, H.E. (author), Noordhoek, J. (author), Blaauboer, B.J. (author)The effects of three acid condensation products of indole-3-carbinol (I3C), i.e. 3,3'-diindolylmethane (DIM), 5,6,11,12,17,18-hexahydrocyclonona[1,2-b:4,5-b:7,8-b]tri-indole (CTI) and 2,3-bis[3-indolylmethyl]indole (BII), on cytochrome P450 and phase II enzymes were studied in primary cultures of rat and cynomolgus monkey liver cells. In rat...article 1992
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Instituut voor Verouderings- en Vaatziekten Onderzoek TNO (author), Horbach, G.J.M.J. (author), van Asten, J.G. (author), Rietjens, I.M.C.M. (author), Kremers, P. (author), van Bezooijen, C.F.A. (author)The content and specific activities of inducible cytochrome P-450 enzymes were determined in liver microscomes of rats of various ages after maximal induction with phenobarbital, isosafrole of 3-methylcholanthrene, and in untreated animals. With age an increase in liver weight was observed both in untreated rats and in maximally induced ones;...article 1992