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Grinberg, M. (author), Stöber, R.M. (author), Edlund, K. (author), Rempel, E. (author), Godoy, P. (author), Reif, R. (author), Widera, A. (author), Madjar, K. (author), Schmidt-Heck, W. (author), Marchan, R. (author), Sachinidis, A. (author), Spitkovsky, D. (author), Hescheler, J. (author), Carmo, H. (author), Arbo, M.D. (author), van de Water, B. (author), Wink, S. (author), Vinken, M. (author), Rogiers, V. (author), Escher, S. (author), Hardy, B. (author), Mitic, D. (author), Myatt, G. (author), Waldmann, T. (author), Mardinoglu, A. (author), Damm, G. (author), Seehofer, D. (author), Nüssler, A. (author), Weiss, T.S. (author), Oberemm, A. (author), Lampen, A. (author), Schaap, M.M. (author), Luijten, M. (author), van Steeg, H. (author), Thasler, W.E. (author), Kleinjans, J.C.S. (author), Stierum, R.H. (author), Leist, M. (author), Rahnenführer, J. (author), Hengstler, J.G. (author)Correction to: Arch Toxicol (2014) 88:2261–2287 https://doi.org/10.1007/s00204-014-1400-x.article 2022
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Stevens, L.J. (author), Donkers, J.M. (author), Dubbel, J. (author), Vaes, W.H.J. (author), van de Steeg, E. (author), Knibbe, C.A.J. (author), Alwayn, I.P.J. (author), van de Steeg, E. (author)To predict the absorption, distribution, metabolism and excretion (ADME) profile of candidate drugs a variety of preclinical models can be applied. The ADME and toxicological behavior of newly developed drugs are often investigated prior to assessment in humans, which is associated with long time-lines and high costs. Therefore, good predictions...article 2020
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van Bilsen, J.H.M. (author), Dulos, R. (author), van Stee, M.F. (author), Meima, M.Y. (author), Rouhani Rankouhi, T. (author), Neergaard Jacobsen, L. (author), Staudt Kvistgaard, A. (author), Garthoff, J.A. (author), Knippels, L.M.J. (author), Knipping, K. (author), Houben, G.F. (author), Verschuren, L. (author), Meijerink, M. (author), Krishnan, S. (author)A healthy immune status is strongly conditioned during early life stages. Insights into the molecular drivers of early life immune development and function are prerequisite to identify strategies to enhance immune health. Even though several starting points for targeted immune modulation have been identified and are being developed into...article 2020
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Reinen, J. (author), Nematollahi, L. (author), Fidder, A. (author), Vermeulen, N.P.E. (author), Noort, D. (author), Commandeur, J.N.M. (author)Tri-ortho-cresyl phosphate (ToCP) is a multipurpose organophosphorus compound that is neurotoxic and suspected to be involved in aerotoxic syndrome in humans. It has been reported that not ToCP itself but a metabolite of ToCP, namely, 2-(ortho-cresyl)-4H-1,2,3-benzodioxaphosphoran-2-one (CBDP), may be responsible for this effect as it can...article 2015
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Grinberg, M. (author), Stöber, R.M. (author), Edlund, K. (author), Rempel, E. (author), Godoy, P. (author), Reif, R. (author), Widera, A. (author), Madjar, K. (author), Schmidt-Heck, W. (author), Marchan, R. (author), Sachinidis, A. (author), Spitkovsky, D. (author), Hescheler, J. (author), Carmo, H. (author), Arbo, M.D. (author), van de Water, B. (author), Wink, S. (author), Vinken, M. (author), Rogiers, V. (author), Escher, S. (author), Hardy, B. (author), Mitic, D. (author), Myatt, G. (author), Waldmann, T. (author), Mardinoglu, A. (author), Damm, G. (author), Seehofer, D. (author), Nüssler, A. (author), Weiss, T.S. (author), Oberemm, A. (author), Lampen, A. (author), Schaap, M.M. (author), Luijten, M. (author), van Steeg, H. (author), Thasler, W.E. (author), Kleinjans, J.C.S. (author), Stierum, R.H. (author), Leist, M. (author), Rahnenführer, J. (author), Hengstler, J.G. (author)A long-term goal of numerous research projects is to identify biomarkers for in vitro systems predicting toxicity in vivo. Often, transcriptomics data are used to identify candidates for further evaluation. However, a systematic directory summarizing key features of chemically influenced genes in human hepatocytes is not yet available. To bridge...article 2014
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Beker van Woudenberg, A. (author), Snel, C. (author), Rijkmans, E. (author), de Groot, D. (author), Bouma, M. (author), Hermsen, S. (author), Piersma, A. (author), Menke, A. (author), Wolterbeek, A. (author)To improve the predictability of the zebrafish embryotoxicity test (ZET) for developmental (neuro)toxicity screening, we used a multiple-endpoints strategy, including morphology, motor activity (MA), histopathology and kinetics. The model compounds used were antiepileptic drugs (AEDs): valproic acid (VPA), carbamazepine (CBZ), ethosuximide (ETH)...article 2014
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Wopereis, S. (author), Radonjic, M. (author), Rubingh, C. (author), van Erk, M. (author), Smilde, A. (author), van Duyvenvoorde, W. (author), Cnubben, N. (author), Kooistra, T. (author), van Ommen, B. (author), Kleemann, R. (author)The prevalence of diabetes mellitus Type 2 could be significantly reduced by early identification of subjects at risk, allowing for better prevention and earlier treatment. Glucose intolerance (GI) is a hallmark of the prediabetic stage. This study aims at identifying 1) prognostic biomarkers predicting the risk of developing GI later in life...article 2012
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Smits, K.M. (author), Schouten, L.J. (author), van Dijk, B.A.C. (author), van Houwelingen, K. (author), van de Hulsbergen-Kaa, C.A. (author), Kiemeney, L.A.L.M. (author), van Houwelingen, K. (author), Goldbohm, R.A. (author), Oosterwijk, E. (author), van den Brandt, P.A. (author), TNO Kwaliteit van Leven (author)Metabolic gene polymorphisms have previously been suggested as risk factors for renal cell carcinoma (RCC). These polymorphisms are involved in activation or detoxification of carcinogens in cigarette smoke which is another RCC risk factor. We evaluated gene-environment interactions between CYP1A1, GSTμ1 and smoking in a large population-based...article 2008
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Hogervorst, J.G.F. (author), Schouten, L.J. (author), Konings, E.J.M. (author), Goldbohm, R.A. (author), van den Brandt, P.A. (author), TNO Kwaliteit van Leven (author)Acrylamide is a probable human carcinogen that was detected in several heat-treated foods, such as French fries and crisps, in 2002. Prospective studies are needed on acrylamide and human cancer risk. We prospectively investigated the association between acrylamide and gastrointestinal cancer risk. In 1986, 120,852 men and women (aged 55-69 y)...article 2008
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Price, R.J. (author), Scott, M.P. (author), Giddings, A.M. (author), Walters, D.G. (author), Stierum, R.H. (author), Meredith, C. (author), Lake, B.G. (author), TNO Kwaliteit van Leven (author)1. The objective of this study was to investigate the effects of four food chemicals, namely butylated hydroxytoluene (BHT), curcumin (CC), propyl gallate (PG) and thiabendazole (TB), on cytochrome P450 (CYP) forms in cultured human hepatocytes. 2. Treatment of human hepatocytes for 72 h with 2-200 μM TB produced concentration-dependent...article 2008
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Stierum, R. (author), Conesa, A. (author), Heijne, W. (author), Ommen, B.v. (author), Junker, K. (author), Scott, M.P. (author), Price, R.J. (author), Meredith, C. (author), Lake, B.G. (author), Groten, J. (author), TNO Kwaliteit van Leven (author), KvL (author)Transcriptomics was performed to gain insight into mechanisms of food additives butylated hydroxytoluene (BHT), curcumin (CC), propyl gallate (PG), and thiabendazole (TB), additives for which interactions in the liver can not be excluded. Additives were administered in diets for 28 days to Sprague-Dawley rats and cDNA microarray experiments were...article 2008
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Jacobs, M.N. (author), Janssens, W. (author), Bernauer, U. (author), Brandon, E. (author), Coecke, S. (author), Combes, R. (author), Edwards, P. (author), Freidig, A. (author), Freyberger, A. (author), Kolanczyk, R. (author), Mc Ardie, C. (author), Mekenyan, O. (author), Schmieder, P. (author), Schrader, T. (author), Takeyoshi, M. (author), van der Burg, B. (author), TNO Kwaliteit van Leven (author)Legislation and prospective legislative proposals in for instance the USA, Europe, and Japan require, or may require that chemicals are tested for their ability to disrupt the hormonal systems of mammals. Chemicals found to test positive are considered to be endocrine active substances (EAS) and may be putative endocrine disruptors (EDs). To...article 2008
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Damsten, M.C. (author), Commandeur, J.N.M. (author), Fidder, A. (author), Hulst, A.G. (author), Touw, D. (author), Noort, D. (author), Vermeulen, N.P.E. (author), TNO Defensie en Veiligheid (author)Covalent binding of reactive electrophilic intermediates to proteins is considered to play an important role in the processes leading to adverse drug reactions and idiosyncratic drug reactions. Consequently, both for the discovery and the development of new drugs, there is a great interest in sensitive methodologies that enable the detection of...article 2007
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Gibbs, S. (author), van de Sandt, J.J.M. (author), Merk, H.F. (author), Lockley, D.J. (author), Pendlington, R.U. (author), Pease, C.K. (author), TNO Kwaliteit van Leven (author)In this review, we discuss and compare studies of xenobiotic metabolism in both human skin and 3D human skin reconstructs. In comparison to the liver, the skin is a less studied organ in terms of characterising metabolic capability. While the skin forms the major protective barrier to environmental chemical exposure, it is also a potential...article 2007
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Ruijssenaars, H.J. (author), Sperling, E.M.G.M. (author), Wiegerinck, P.H.G. (author), Brands, F.T.L. (author), Wery, J. (author), de Bont, J.A.M. (author), TNO Kwaliteit van Leven (author)A steroid 15β-hydroxylating whole-cell solvent tolerant biocatalyst was constructed by expressing the Bacillus megaterium steroid hydroxylase CYP106A2 in the solvent tolerant Pseudomonas putida S12. Testosterone hydroxylation was improved by a factor 16 by co-expressing Fer, a putative Fe-S protein from Bacillus subtilis. In addition, the...article 2007
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Jeurissen, S.M.F. (author), Claassen, F.W. (author), Havlik, J. (author), Bouwmans, E.E. (author), Cnubben, N.H.P. (author), Sudhölter, E.J.R. (author), Rietjens, I.M.C.M. (author), van Beek, T.A. (author), TNO Kwaliteit van Leven (author)An on-line HPLC screening method for detection of inhibitors of human cytochrome P450 1A2 in extracts was developed. HPLC separation of extracts is connected to a continuous methoxyresorufin-O-demethylation (MROD) assay in which recombinant human P450 1A2 converts methoxyresorufin to its fluorescent metabolite resorufin. The system was tested...article 2007
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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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Kienhuis, A.S. (author), Wortelboer, H.M. (author), Maas, W.J. (author), van Herwijnen, M. (author), Kleinjans, J.C.S. (author), van Delft, J.H.M. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author)A rapid decline of cytochrome P450 (CYP450) enzyme activities remains a drawback of rat hepatocyte-based in vitro cultures. Consequently, judgment of the toxic potential of compounds that need bioactivation by CYP450s may not be adequate using this model. In the present study, an improved hepatocyte-based in vitro system was developed with...article 2007
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Kienhuis, A.S. (author), Wortelboer, H.M. (author), Hoflack, J.C. (author), Moonen, E.J. (author), Kleinjans, J.C.S. (author), van Ommen, B. (author), van Delft, J.H.M. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author)Sandwich-cultured primary rat hepatocytes are often used as an in vitro model in toxicology and pharmacology. However, loss of liver-specific functions, in particular, the decline of cytochrome P450 (P450) enzyme activity, limits the value of this model for prediction of in vivo toxicity. In this study, we investigated whether a hepatic in vitro...article 2006
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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