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Schutte, M.E. (author), Boersma, M.G. (author), Verhallen, D.A.M. (author), Groten, J.P. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)This study describes and kinetically models the effect of flavonoid mixtures on PhIP transport through Caco-2 monolayers. Previously it was shown that quercetin, luteolin, naringenin and myricetin increase the apical to basolateral PhIP transport in Caco-2 monolayers. In this study, apigenin was shown to exert a similar effect with an apparent...article 2008
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Schutte, M.E. (author), Alink, G.M. (author), Freidig, A.P. (author), Spenkelink, B. (author), Vaessen, J.C.H. (author), van de Sandt, J.J.M. (author), Groten, J.P. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author), KvL (author)This study investigates whether the previous observation that quercetin increases the transport of PhIP through Caco-2 monolayers in vitro could be confirmed in an in vivo rat model. Co-administration of 1.45 μmol PhIP/kg bw and 30 μmol quercetin/kg bw significantly increased the blood AUC(0-8 h) of PhIP in rats to 131 ± 14% of the AUC(0-8 h)...article 2008
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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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Schutte, M.E. (author), Freidig, A.P. (author), van de Sandt, J.J.M. (author), Alink, G.M. (author), Rietjens, I.M.C.M. (author), Groten, J.P. (author), TNO Kwaliteit van Leven (author)The present study describes the effect of different flavonoids on the absorption of the pro-carcinogen PhIP through Caco-2 monolayers and the development of an in silico model describing this process taking into account passive diffusion and active transport of PhIP. Various flavonoids stimulated the apical to basolateral PhIP transport. Using...article 2006
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Brand, W. (author), Schutte, M.E. (author), Williamson, G. (author), van Zanden, J.J. (author), Cnubben, N.H.P. (author), Groten, J.P. (author), van Bladeren, P.J. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)The transcellular transport of ingested food ingredients across the intestinal epithelial barrier is an important factor determining bioavailability upon oral intake. This transcellular transport of many chemicals, food ingredients, drugs or toxic compounds over the intestinal epithelium can be highly dependent on the activity of membrane bound...article 2006
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Verwei, M. (author), Freidig, A.P. (author), Havenaar, R. (author), Groten, J.P. (author), TNO Kwaliteit van Leven (author)The nutritional quality of new functional or fortified food products depends on the bioavailability of the nutrient(s) in the human body. Bioavailability is often determined in human intervention studies by measurements of plasma or serum profiles over a certain time period. These studies are time and cost consuming and often appear to lack an...article 2006
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Schutte, M.E. (author), van de Sandt, J.J.M. (author), Alink, G.M. (author), Groten, J.P. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)The effect of the flavonoid myricetin on the transport of the pro-carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through differentiated Caco-2 monolayers, a model for the intestinal epithelium, is described. Myricetin causes an increase of the transport of PhIP from the apical to the basolateral compartment. This effect was...article 2006
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Heijne, W.H.M. (author), Jonker, D. (author), Stierum, R.H. (author), van Ommen, B. (author), Groten, J.P. (author), TNO Kwaliteit van Leven (author)Benzene is an industrial chemical, component of automobile exhaust and cigarette smoke. After hepatic bioactivation benzene induces bone marrow, blood and hepatic toxicity. Using a toxicogenomics approach this study analysed the effects of benzene at three dose levels on gene expression in the liver after 28 daily doses. NMR based metabolomics...article 2005
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Verwei, M. (author), van den Berg, H. (author), Havenaar, R. (author), Groten, J.P. (author), TNO Defensie en Veiligheid TNO Kwaliteit van Leven (author)Background: Milk products are a potential matrix for fortification with synthetic folic acid or natural 5-methyltetrahydrofolate (5-CH 3-H4folate) to enhance the daily folate intake. In milk, folate occurs bound to folatebinding proteins (FBP). Our previous studies with an in vitro gastrointestinal model showed that 70% of the initial FBP...article 2005
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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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- Verwei, M. (author), Arkbåge, K. (author), Groten, J.P. (author), Witthöft, C. (author), van den Berg, H. (author), Havenaar, R. (author), TNO Defensie en Veiligheid TNO Kwaliteit van Leven (author) article 2005
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TNO Kwaliteit van Leven (author), Heijne, W.H.M. (author), Kienhuis, A.S. (author), vnn Ommen, B. (author), Stierum, R.H. (author), Groten, J.P. (author)Toxicogenomics can facilitate the identification and characterization of toxicity, as illustrated in this review. Toxicogenomics, the application of the functional genomics technologies (transcriptomics, proteomics and metabolomics) in toxicology enables the study of adverse effects of xenobiotic substances in relation to structure and activity...article 2005
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- Groten, J.P. (author), Heijne, W.H.M. (author), Stierum, R.H. (author), Freidig, A.P. (author), Feron, V.J. (author), TNO Voeding (author) article 2004
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Jonker, D. (author), Freidig, A.P. (author), Groten, J.P. (author), de Hollander, A.E.M. (author), Stierum, R.H. (author), Woutersen, R.A. (author), Feron, V.J. (author), TNO Voeding (author)Recent developments in hazard identification and risk assessment of chemical mixtures are reviewed. Empirical, descriptive approaches to study and characterize the toxicity of mixtures have dominated during the past two decades, but an increasing number of mechanistic approaches have made their entry into mixture toxicology. A series of...article 2004
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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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Price, R.J. (author), Scott, M.P. (author), Walters, D.G. (author), Stierum, R.H. (author), Groten, J.P. (author), Meredith, C. (author), Lake, B.G. (author), TNO Voeding (author)The effect of thiabendazole (TB) on some rat hepatic xenobiotic metabolising enzymes has been investigated. Male Sprague-Dawley rats were fed control diet or diets containing 102-5188 ppm TB for 28 days. As a positive control for induction of hepatic xenobiotic metabolism, rats were also fed diets containing 1457 and 10,155 ppm butylated...article 2004
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- Ommen, B. (author), Groten, J.P. (author), TNO Voeding (author) article 2004
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Oomen, A.G. (author), Tolls, J. (author), Sips, A.J.A.M. (author), Groten, J.P. (author)Children might be exposed substantially to contaminants such as lead via soil ingestion. In risk assessment of soil contaminants there is a need for information on oral bioavailability of soilborne lead. Oral bioavailability can be seen as the result of four steps: (1) soil ingestion; (2) mobilization from soil during digestion, i.e.,...article 2003
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Feron, V.J. (author), Groten, J.P. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)This paper addresses major developments in the safety evaluation of chemical mixtures during the past 15 years, reviews today's state of the art of mixture toxicology, and discusses challenges ahead. Well-thought-out tailor-made mechanistic and empirical designs for studying the toxicity of mixtures have gradually substituted trial-and-error...article 2002
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Feron, V.J. (author), Cassee, F.R. (author), Groten, J.P. (author), van Vliet, P.W. (author), van Zorge, J.A. (author), TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO (author)In this article, we highlight new developments and recent studies concerning adverse human health effects related to chemical mixtures. One group of activities comprises the development of a new computer program for analyzing mixture studies and a mathematical model as a basis for combination rules that predict the toxicity of mixtures. Other...article 2002