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Kienhuis, A.S. (author), van de Poll, M.C.G. (author), Wortelboer, H. (author), van Herwijnen, M. (author), Gottschalk, R. (author), de Jong, C.H.C. (author), Boorsma, A. (author), Paules, R.S. (author), Kleinjans, J.C.S. (author), Stierum, R.H. (author), van Delft, J.H.M. (author), TNO Kwaliteit van Leven (author)The frequent use of rodent hepatic in vitro systems in pharmacological and toxicological investigations challenges extrapolation of in vitro results to the situation in vivo and interspecies extrapolation from rodents to humans. The toxicogenomics approach may aid in evaluating relevance of these model systems for human risk assessment by direct...article 2009
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Schoonen, W.G.E.J. (author), Kloks, C.P.A.M. (author), Ploemen, J.P.H.T.M. (author), Horbach, G.J. (author), Smit, M.J. (author), Zandberg, P. (author), Mellema, J.R. (author), van Zuylen, C.T. (author), Tas, A.C. (author), van Nesselrooij, J.H.J. (author), Vogels, J.T.W.E. (author), TNO Kwaliteit van Leven (author)1H nuclear magnetic resonance (NMR) spectroscopy of rat urine in combination with pattern recognition analysis was evaluated for early noninvasive detection of toxicity of investigational chemical entities. Bromobenzene (B) and paracetamol (P) were administered at five single oral dosages between 2 and 500 mg/kg and between 6 and 1800 mg/kg,...article 2007
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Schoonen, W.G.E.J. (author), Kloks, C.P.A.M. (author), Ploemen, J.-P.H.T.M. (author), Smit, M.J. (author), Zandberg, P. (author), Horbach, G.J. (author), Mellema, J.-R. (author), van Zuylen, C.T. (author), Tas, A.C. (author), van Nesselrooij, J.H.J. (author), Vogels, J.T.W.E. (author), TNO Kwaliteit van Leven (author)A procedure of nuclear magnetic resonance (NMR) urinalysis using pattern recognition is proposed for early detection of toxicity of investigational compounds in rats. The method is applied to detect toxicity upon administration of 13 toxic reference compounds and one nontoxic control compound (mianserine) in rats. The toxic compounds are...article 2007
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Heijne, W.H.M. (author), Lamers, R.J.A.N. (author), van Bladeren, P.J. (author), Groten, J.P. (author), van Nesselrooij, J.H.J. (author), van Ommen, B. (author), TNO Kwaliteit van Leven (author)This study investigated whether integrated analysis of transcriptomics and metabolomics data increased the sensitivity of detection and provided new insight in the mechanisms of hepatotoxicity. Metabolite levels in plasma or urine were analyzed in relation to changes in hepatic gene expression in rats that received bromobenzene to induce acute...article 2005
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Heijne, W.H.M. (author), Slitt, A.L. (author), van Bladeren, P.J. (author), Groten, J.P. (author), Klaassen, C.D. (author), Stierum, R.H. (author), van Ommen, B. (author), TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO (author)Rats were exposed to three levels of bromobenzene, sampled at 6, 24, and 48 h, and liver gene expression profiles were determined to identify dose and time-related changes. Expression of many genes changed transiently, and dependent on the dose. Few changes were identified after 6 h, but many genes were differentially expressed after 24 h, while...article 2004
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Hoebe, K.H.N. (author), Witkamp, R.F. (author), Fink-Gremmels, J. (author), van Miert, A.S.J.P.A.M. (author), Monshouwer, M. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)This study focuses on the importance of direct contact between Kupffer cells (KCs) and hepatocytes (HCs) during the hepatic inflammatory response using an in vitro approach. The lipopolysaccharide (LPS)-induced inflammatory response in monocultures of porcine HCs and KCs were compared with cocultures prepared either with direct contact between...article 2001