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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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Kuper, C.F. (author), Stierum, R.H. (author), Boorsma, A. (author), Schijf, M.A. (author), Prinsen, M. (author), Bruijntjes, J.P. (author), Bloksma, N. (author), Arts, J.H.E. (author), TNO Kwaliteit van Leven (author)
All LMW respiratory allergens known to date can also induce skin allergy in test animals. The question here was if in turn skin allergens can induce allergy in the respiratory tract. Respiratory allergy was tested in Th2-prone Brown Norway (BN) rats by dermal sensitization with the contact allergen dinitrochlorobenzene (DNCB; 1%, day 0; 0.5%,...
article 2008
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Dihal, A.A. (author), van der Woude, H. (author), Hendriksen, P.J.M. (author), Charif, H. (author), Dekker, L.J. (author), IJsselstijn, L. (author), de Boer, V.C.J. (author), Alink, G.M. (author), Burgers, P.C. (author), Rietjens, I.M.C.M. (author), Woutersen, R.A. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author), KvL (author)
Quercetin has been shown to act as an anticarcinogen in experimental colorectal cancer (CRC). The aim of the present study was to characterize transcriptome and proteome changes occurring in the distal colon mucosa of rats supplemented with 10 g quercetin/kg diet for 11 wk. Transcriptome data analyzed with Gene Set Enrichment Analysis showed...
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
document
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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Dihal, A.A. (author), Tilburgs, C. (author), van Erk, M.J. (author), Rietjens, I.M.C.M. (author), Woutersen, R.A. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author)
The aim was to investigate mechanisms contributing to quercetin's previously described effects on cell-proliferation and -differentiation, which contradicted its proposed anticarcinogenic potency. In a 10-day experiment, 40 μM quercetin stabilized by 1 mM ascorbate reduced Caco-2 differentiation up to 50% (p < 0.001). Caco-2 RNA from days 5 and...
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
document
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
document
Dihal, A.A. (author), de Boer, V.C.J. (author), van der Woude, H. (author), Tilburgs, C. (author), Bruijntjes, J.P. (author), Alink, G.M. (author), Rietjens, I.M.C.M. (author), Woutersen, R.A. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author)
The effect of the flavonoid quercetin and its conjugate rutin was investigated on (biomarkers of) colorectal cancer (CRC). Male F344 rats (n = 42/group) were fed 0, 0.1, 1, or 10 g quercetin/kg diet or 40 g rutin/kg diet. Two wk after initial administration of experimental diets, rats were given 2 weekly subcutaneous injections with 15 mg/kg...
article 2006
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Dihal, A.A. (author), Woutersen, R.A. (author), Ommen, B.v. (author), Rietjens, I.M.C.M. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author)
The effect of the dietary flavonoid quercetin was investigated on proliferation and differentiation of the human colon cancer cell line Caco-2. Confluent Caco-2 monolayers exposed to quercetin showed a biphasic effect on cell proliferation and a decrease in cell differentiation (0.001<P<0.05). During differentiation Caco-2 cells formed 5 phase...
article 2006
document
van Erk, M.J. (author), Roepman, P. (author), van der Lende, T.R. (author), Stierum, R.H. (author), Aarts, J.M.M.J.G. (author), van Bladeren, P.J. (author), van Ommen, B. (author), TNO Kwaliteit van Leven (author)
Background: Many different mechanisms are involved in nutrient-related prevention of colon cancer. In this study, a comprehensive assessment of the spectrum of possible biological actions of the bioactive compound quercetin is made using multiple gene expression analysis. Quercetin is a flavonoid that can inhibit proliferation of tumor cells and...
article 2005
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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
document
Heijne, W.H.M. (author), Stierum, R.H. (author), Slijper, M. (author), van Bladeren, P.J. (author), van Ommen, B. (author)
Toxicogenomics is a novel approach integrating the expression analysis of thousands of genes (transcriptomics) or proteins (proteomics) with classical methods in toxicology. Effects at the molecular level are related to pathophysiological changes of the organisms, enabling detailed comparison of mechanisms and early detection and prediction of...
article 2003
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Stierum, R. (author), Gaspari, M. (author), Dommels, Y. (author), Ouatas, T. (author), Pluk, H. (author), Jespersen, S. (author), Vogels, J. (author), Verhoeckx, K. (author), Groten, J. (author), van Ommen, B. (author)
Here, we describe a proteomics approach to study protein expression changes in differentiating Caco-2 cells. Caco-2 is a colorectal carcinoma cell line, which upon differentiation loses its tumorigenic phenotype and displays characteristics of mature enterocytes, including brush borders with microvilli. Cells were grown in culture flasks and...
article 2003
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