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Human cytochrome P450 enzyme specificity for the bioactivation of estragole and related alkenylbenzenes

Jeurissen, S.M.F. (author), Punt, A. (author), Boersma, M.G. (author), Bogaards, J.J.P. (author), Fiamegos, Y.C. (author), Schilter, B. (author), van Bladeren, P.J. (author), Cnubben, N.H.P. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)

Human cytochrome P450 enzymes involved in the bioactivation of estragole to its proximate carcinogen 1′-hydroxyestragole were identified and compared to the enzymes of importance for 1′-hydroxylation of the related alkenylbenzenes methyleugenol and safrole. Incubations with Supersomes revealed that all enzymes tested, except P450 2C8, are...

article 2007

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Transcriptomics analysis of interactive effects of benzene, trichloroethylene and methyl mercury within binary and ternary mixtures on the liver and kidney following subchronic exposure in the rat

Hendriksen, P.J.M. (author), Freidig, A.P. (author), Jonker, D. (author), Thissen, U. (author), Bogaards, J.J.P. (author), Mumtaz, M.M. (author), Groten, J.P. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author)

The present research aimed to study the interaction of three chemicals, methyl mercury, benzene and trichloroethylene, on mRNA expression alterations in rat liver and kidney measured by microarray analysis. These compounds were selected based on presumed different modes of action. The chemicals were administered daily for 14 days at the Lowest...

article 2007

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Human cytochrome P450 enzymes of importance for the bioactivation of methyleugenol to the proximate carcinogen 1′-hydroxymethyleugenol

Jeurissen, S.M.F. (author), Bogaards, J.J.P. (author), Boersma, M.G. (author), ter Horst, J.P.F. (author), Awad, H.M. (author), Fiamegos, Y.C. (author), van Beek, T.A. (author), Alink, G.M. (author), Sudhölter, E.J.R. (author), Cnubben, N.H.P. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)

In vitro studies were performed to elucidate the human cytochrome P450 enzymes involved in the bioactivation of methyleugenol to its proximate carcinogen 1′-hydroxymethyleugenol. Incubations with Supersomes, expressing individual P450 enzymes to a high level, revealed that P450 1A2, 2A6, 2C9, 2C19, and 2D6 are intrinsically able to 1′...

article 2006

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The novel antifungal agent PLD-118 is neither metabolized by liver microsomes nor inhibits cytochrome P450 in vitro

Parnham, M.J. (author), Bogaards, J.J.P. (author), Schrander, F. (author), Schut, M.W. (author), Orešković, K. (author), Mildner, B. (author), TNO Kwaliteit van Leven (author)

PLD-118 is a novel, oral antifungal drug, under development for the treatment of Candida infections. Possible metabolism of PLD-118 by rat, dog and human S9 liver homogenates and inhibition of human cytochrome P450 (CYP) enzymes were investigated. PLD-118 (10 and 100 μm) incubated for 0-60 min with S9 fractions and NADPH was determined by HPLC,...

article 2005

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Human cytochrome P450 enzyme specificity for bioactivation of safrole to the proximate carcinogen 1′-hydroxysafrole

Jeurissen, S.M.F. (author), Bogaards, J.J.P. (author), Awad, H.M. (author), Boersma, M.G. (author), Brand, W. (author), Fiamegos, Y.C. (author), van Beek, T.A. (author), Alink, G.M. (author), Sudhölter, E.J.R. (author), Cnubben, N.H.P. (author), Rietjens, I.M.C.M. (author), TNO Voeding (author)

In the present study, the cytochrome P450 mediated bioactivation of safrole to its proximate carcinogenic metabolite, 1′-hydroxysafrole, has been investigated for the purpose of identifying the human P450 enzymes involved. The 1′-hydroxylation of safrole was characterized in a variety of in vitro test systems, including Supersomes, expressing...

article 2004

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The use of in vitro metabolic parameters and physiologically based pharmacokinetic (PBPK) modeling to explore the risk assessment of trichloroethylene

Hissink, E.M. (author), Bogaards, J.J.P. (author), Freidig, A.P. (author), Commandeur, J.N.M. (author), Vermeulen, N.P.E. (author), van Bladeren, P.J. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

A physiologically based pharmacokinetic (PBPK) model has been developed for trichloroethylene (1,1,2-trichloroethene, TRI) for rat and humans, based on in vitro metabolic parameters. These were obtained using individual cytochrome P450 and glutathione S-transferase enzymes. The main enzymes involved both for rats and humans are CYP2E1 and the μ-...

article 2002

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Modelling the responses to biological reactive intermediates: Establishing the borderlines of risk

van Bladeren, P.J. (author), Bogaards, J.J.P. (author), Cnubben, N.H.P. (author), Hissink, E.M. (author), TNO Voeding (author)

conference paper 2001

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Prediction of isoprene diepoxide levels in vivo in mouse, rat and man using enzyme kinetic data in vitro and physiologically-based pharmacokinetic modelling

Bogaards, J.J.P. (author), Freidig, A.P. (author), van Bladeren, P.J. (author), TNO Voeding (author)

The present study was designed to explain the differences in isoprene toxicity between mouse and rat based on the liver concentrations of the assumed toxic metabolite isoprene diepoxide. In addition, extrapolation to the human situation was attempted. For this purpose, enzyme kinetic parameters Km and Vmax were determined in vitro in mouse, rat...

article 2001

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Prediction of interindividual variation in drug plasma levels in vivo from individual enzyme kinetic data and physiologically based pharmacokinetic modeling

Bogaards, J.J.P. (author), Hissink, E.M. (author), Briggs, M. (author), Weaver, R. (author), Jochemsen, R. (author), Jackson, P. (author), Bertrand, M. (author), van Bladeren, P. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

A strategy is presented to predict interindividual variation in drug plasma levels in vivo by the use of physiologically based pharmacokinetic modeling and human in vitro metabolic parameters, obtained through the combined use of microsomes containing single cytochrome P450 enzymes and a human liver microsome bank. The strategy, applied to the...

article 2000

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Determining the best animal model for human cytochrome P450 activities: A comparison of mouse, rat, rabbit, dog, micropig, monkey and man

Bogaards, J.J.P. (author), Bertrand, M. (author), Jackson, P. (author), Oudshoorn, M.J. (author), Weavers, R.J. (author), van Bladeren, P.J. (author), Walther, B. (author)

article 2000

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Conjugation of isoprene monoepoxides with glutathione, catalyzed by α, μ, π and θ-class glutathione S-transferases of rat and man

Bogaards, J.J.P. (author), Venekamp, J.C. (author), Salmon, F.G.C. (author), van Bladeren, P.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

In the present study, the enzymatic conjugation of the isoprene monoepoxides 3,4 epoxy-3-methyl-1-butene (EPOX-I) and 3,4-epoxy-2-methyl-1-butene (EPOX-II) with glutathione was investigated, using purified glutathione S-transferases (GSTs) of the α, μ, π and θ-class of rat and man. HPLC analysis of incubations of EPOX-I and EPOX-II with [35S...

article 1999

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Conjugation of isoprene monoepoxides with glutathione, catalyzed by alpha, mu, pie and teta-class glutathione S-transferases of rat and man

Bogaards, J.J.P. (author), Venekamp, J.C. (author), Salmon, F.G.C. (author), van Bladeren, P.J. (author)

article 1999

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In vitro and in vivo studies on the disposition of mirtazapine in humans

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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Effect of short-term dietary administration of eugenol in humans

Rompelberg, C.J.M. (author), Vogels, J.T.W.E. (author), de Vogel, N. (author), Bruijntjes-Rozier, G.C.D.M. (author), Stenhuis, W.H. (author), Bogaards, J.J.P. (author), Verhagen, H. (author), TNO Voeding (author)

1. In order to study the antigenotoxic potential of eugenol in humans, ten healthy non-smoking males ingested a daily amount of 150 mg eugenol or the placebo for seven consecutive days. After a washout period of one week, groups ingesting eugenol or the placebo were crossed and received the other treatment for seven consecutive days. 2. On days...

article 1996

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Effect of a vegan diet on biomarkers of chemoprevention in females

Verhagen, H. (author), Rauma, A.L. (author), Törrönen, R. (author), de Vogel, N. (author), Bruijntjes-Rozier, G.C.D.M. (author), Dreve, M.A. (author), Bogaards, J.J.P. (author), Mykkänen, H. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

1. In order to study the potential beneficial effects of a vegan diet, a cross-sectional study was performed and several biomarkers of chemoprevention were measured in a population of female 'living food' eaters ('vegans'; n = 20) vs matched omnivorous controls (n = 20). 2. White blood cells obtained from fresh blood samples were subjected to...

article 1996

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The biotransformation of isoprene and the two isoprene monoepoxides by human cytochrome P450 enzymes, compared to mouse and rat liver microsomes

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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Human cytochrome P450 enzyme selectivities in the oxidation of chlorinated benzenes

Bogaards, J.J.P. (author), van Ommen, B. (author), Wolf, C.R. (author), van Bladeren, P.J. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

1,2-Dichlorobenzene 1,4-dichlorobenzene, 1,2,4-trichlorobenzene, 1,2,3,5-tetrachlorobenzene, and pentachlorobenzene were incubated with microsomes derived from cell lines expressing human CYP1A1, CYP1A2, CYP3A4, CYP2E1, or CYP2D6. The formation of phenolic metabolites as determined by gas chromatographic analysis evealed that CYP2E1 possessed...

article 1995

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Some principles of combination toxicology applied to defined mixtures of (chlorinated organic) chemicals

Feron, V.J. (author), Jonker, D. (author), van den Berg, M. (author), Bogaards, J.J.P. (author), Groten, J.P. (author), Bladeren, P.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

conference paper 1995

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Cancer-preventing potential of natural food constituents

Verhagen, H. (author), van Poppel, G. (author), Willems, M.I. (author), Bogaards, J.J.P. (author), Rompelberg, C.J.M. (author), van de Kerkhof, M.C.A. (author), van Bladeren, P.J. (author)

conference paper 1993

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Purification and characterization of eight glutathione S-transferase isoenzymes of hamster: comparison of subunit composition of enzymes from liver, kidney, testis, pancreas and trachea

Instituut CIVO-Toxicologie en Voeding TNO (author), Bogaards, J.J.P. (author), van Ommen, B. (author), van Bladeren, P.J. (author)

Eight dimeric isoenzymes of glutathione S-transferase (GST) were purified from liver, kidney and testis of the Syrian golden hamster, using S-hexylglutathione affinity chromatography and chromatofocusing. The isoenzymes were characterized according to their substrate selectivity, physical properties and amino acid sequence analysis. Thus a...

article 1992