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The transferability from rat subacute 4-week oral toxicity study to translational research exemplified by two pharmaceutical immunosuppressants and two environmental pollutants with immunomodulating properties

Kemmerling, J. (author), Fehlert, E. (author), Kuper, C.F. (author), Rühl-Fehlert, C. (author), Stropp, G. (author), Vogels, J. (author), Krul, C. (author), Vohr, H.W. (author)

Exposure to chemicals may have an influence on the immune system. Often, this is an unwanted effect but in some pharmaceuticals, it is the intended mechanism of action. Immune function tests and in depth histopathological investigations of immune organs were integrated in rodent toxicity studies performed according to an extended OECD test...

article 2015

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Time series analysis of benzo[a]pyrene-induced transcriptome changes suggests that a network of transcription factors regulates the effects on functional gene sets

van Delft, J.H.M. (author), Mathijs, K. (author), Staal, Y.C.M. (author), van Herwijnen, M.H.M. (author), Brauers, K.J.J. (author), Boorsma, A. (author), Kleinjans, J.C.S. (author), TNO Kwaliteit van Leven (author)

Chemical carcinogens may cause a multitude of effects inside cells, thereby affecting transcript levels of genes by direct activation of transcription factors (TF) or indirectly through the formation of DNA damage. As the temporal profiles of these responses may be profoundly different, examining time-dependent changes may provide new insights...

article 2010

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Relative absorption and dermal loading of chemical substances: Consequences for risk assessment

Buist, H.E. (author), Schaafsma, G. (author), van de Sandt, J.J.M. (author), TNO Kwaliteit van Leven (author)

Quantification of skin absorption is an essential step in reducing the uncertainty of dermal risk assessment. Data from literature indicate that the relative dermal absorption of substances is dependent on dermal loading. Therefore, an internal exposure calculated with absorption data determined at a dermal loading not comparable to the actual...

article 2009

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Interlaboratory and interplatform comparison of microarray gene expression analysis of HepG2 cells exposed to benzo(a)pyrene

Hockley, S.L. (author), Mathijs, K. (author), Staal, Y.C.M. (author), Brewer, D. (author), Giddings, I. (author), van Delft, J.H.M. (author), Phillips, D.H. (author), TNO Kwaliteit van Leven (author)

Microarray technology is being used increasingly to study gene expression of biological systems on a large scale. Both interlaboratory and interplatform differences are known to contribute to variability in microarray data. In this study we have investigated data from different platforms and laboratories on the transcriptomic profile of HepG2...

article 2009

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Interactions between polycyclic aromatic hydrocarbons in binary mixtures: Effects on gene expression and DNA adduct formation in precision-cut rat liver slices

Staal, Y.C.M. (author), Pushparajah, D.S. (author), van Herwijnen, M.H.M. (author), Gottschalk, R.W.H. (author), Maas, L.M. (author), Ioannides, C. (author), van Schooten, F.J. (author), van Delft, J.H.M. (author), TNO Kwaliteit van Leven (author)

Although exposure to polycyclic aromatic hydrocarbons (PAHs) occurs mostly through mixtures, hazard and risk assessment are mostly based on the effects caused by individual compounds. The objective of the current study was to investigate whether interactions between PAHs occur, focusing on gene expression (as measured by cDNA microarrays) and...

article 2008

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The carcinoGENOMICS project: Critical selection of model compounds for the development of omics-based in vitro carcinogenicity screening assays

Vinken, M. (author), Doktorova, T. (author), Ellinger-Ziegelbauer, H. (author), Ahr, H.-J. (author), Lock, E. (author), Carmichael, P. (author), Roggen, E. (author), van Delft, J. (author), Kleinjans, J. (author), Castell, J. (author), Bort, R. (author), Donato, T. (author), Ryan, M. (author), Corvi, R. (author), Keun, H. (author), Ebbels, T. (author), Athersuch, T. (author), Sansone, S.-A. (author), Rocca-Serra, P. (author), Stierum, R. (author), Jennings, P. (author), Pfaller, W. (author), Gmuender, H. (author), Vanhaecke, T. (author), Rogiers, V. (author), TNO Kwaliteit van Leven (author)

Recent changes in the European legislation of chemical-related substances have forced the scientific community to speed up the search for alternative methods that could partly or fully replace animal experimentation. The Sixth Framework Program project carcinoGENOMICS was specifically raised to develop omics-based in vitro screens for testing...

article 2008

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Binary PAH mixtures cause additive or antagonistic effects on gene expression but synergistic effects on DNA adduct formation

Staal, Y.C.M. (author), Hebels, D.G.A.J. (author), van Herwijnen, M.H.M. (author), Gottschalk, R.W.H. (author), van Schooten, F.J. (author), van Delft, J.H.M. (author), TNO Kwaliteit van Leven (author)

Polycyclic aromatic hydrocarbons (PAHs) cover a wide range of structurally related compounds which differ greatly in their carcinogenic potency. PAH exposure usually occurs through mixtures rather than individual compounds. Therefore, we assessed whether the effects of binary PAH mixtures on gene expression, DNA adduct formation, apoptosis and...

article 2007

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Evaluation of Simple Treat 3.0 for two hydrophobic and slowly biodegradable chemicals: Polycyclic musks HHCB and AHTN

Artola-Garicano, E. (author), Hermens, J.L.M. (author), Vaes, W.H.J. (author)

In the current study, predictions by Simple Treat 3.0, a fate model for organic chemicals in sewage treatment plants (STPs), are compared with actual measurements in three STPs. Two polycyclic musks, Tonalide® (AHTN) and Galaxolide® (HHCB), were used for model evaluation. Results show that Simple Treat 3.0 is able to predict the removal...

article 2003

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Exposure-route-dependent DNA adduct formation by polycyclic aromatic hydrocarbons

Godschalk, R.W.L. (author), Moonen, E.J.C. (author), Schilderman, A.E.L. (author), Broekmans, W.M.R. (author), Kleinjans, J.C.S. (author), van Schooten, F.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

Understanding the kinetics of aromatic-DNA adducts in target tissues and white blood cells (WBC) would enhance the applicability of DNA adducts in WBC as surrogate source of DNA in biomonitoring studies. In the present study, rats were acutely exposed to benzo[a]pyrene (B[a]P; 10 mg/kg body wt) via intratracheal (i.t.), dermal and oral...

article 2000

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Comparison of immunoaffinity chromatography enrichment and nuclease P1 procedures for 32P-postlabelling analysis of PAH- DNA adducts

Randerath, K. (author), Sriram, P. (author), Moorthy, B. (author), Aston, J.P. (author), Baan, R.A. (author), van den Berg, P.T.M. (author), Booth, E.D. (author), Watson, W.P. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

32P-postlabelling analysis for detecting DNA adducts formed by polycyclic aromatic compounds is one of the most widely used techniques for assessing genotoxicity associated with these compounds. In cases where the formation of adducts is extremely low, a crucial step in the analysis is an enrichment procedure for adducts prior to the...

article 1998

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Monitoring of occupational exposure to polycyclic aromatic hydrocarbons in a carbon-electrode manufacturing plant

van Delft, J.H.M. (author), Steenwinkel, M-J.S.T. (author), van Asten, J.G. (author), van Es, J. (author), Kraak, A. (author), Baan, R.A. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

An investigation is presented of occupational exposure to polycyclic aromatic hydrocarbons (PAH) in a carbon-electrode manufacturing plant, as assessed by three monitoring methods, viz, environmental monitoring of the external dose by analysis of personal air samples, biological monitoring of the internal dose by analysis of urinary 1...

article 1998

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Influence of growth factors and medium composition on benzo[a]pyrene- and vitamin A-induced cell proliferation and differentiation in hamster tracheal epithelium in organ culture

Wolterbeek, A.P.M. (author), Ciotti, M.A.L.T. (author), Schoevers, E.J. (author), Roggeband, R. (author), Baan, R.A. (author), Feron, V.J. (author), Rutten, A.A.J.J.L. (author), TNO Voeding (author)

Tracheal organ cultures and isolated tracheal epithelial cells are frequently used to study effects of carcinogens and retinoids on both proliferation and differentiation of respiratory tract epithelial cells. For each of these in vitro models, optimal culture conditions have been established, varying in type of culture medium and composition of...

article 1996

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Effect of eugenol on the mutagenicity of benzo[a]pyrene and the formation of benzo[a]pyrene-DNA adducts in the X-lacZ-transgenic mouse.

Rompelberg, C.J.M. (author), Steenwinkel, M.J.S.T. (author), van Asten, J.G. (author), van Delft, J.H.M. (author), Baan, R.A. (author), Verhagen, H. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

To study the possible reduction by eugenol of the mutagenicity and genotoxicity of benzoja]pyrene (B[a]P) in vivo, the X-lacZ-transgenic mouse strain 40.6 (Muta(TM)Mouse) was used. Male mice were fed a diet containing 0.4% (w/w) eugenol or a control diet for 58 days. On day 10, half of the mice received an i.p. dose of 100 mg/kg b.w. B[a]P. The...

article 1996

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Effect of eugenol on the genotoxicity of established mutagens in the liver

Rompelberg, C.J.M. (author), Evertz, S.J.C.J. (author), Bruijntjes-Rozier, G.C.D.M. (author), van den Heuvel, P.D. (author), Verhagen, H. (author), TNO Voeding (author)

The influence of in vivo treatment with eugenol on established mutagens was studied to determine whether eugenol has antigenotoxic potential. The effects of eugenol in rats was investigated in the unscheduled DNA synthesis (UDS) assay with established mutagens and the Salmonella typhimurium mutagenicity assay. In addition, the effect of in vitro...

article 1996

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Ca2+ strongly modulates the effect of vitamin A on benzo[a]pyrene-induced cell proliferation in hamster tracheal epithelium in organ culture

Wolterbeek, A.P.M. (author), Ciotti, M.A.L.T. (author), Schoevers, E.J. (author), Feron, V.J. (author), Rutten, A.A.J.J.L. (author), TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO (author)

Chemicals/CAS: benzo[a]pyrene, 50-32-8; calcium ion, 14127-61-8; retinol, 68-26-8, 82445-97-4

article 1996

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Comparison of the X-gal- and P-gal-based systems for screening of mutant λlacZ phages originating from the transgenic mouse strain 40.6

Mientjes, E.J. (author), Steenwinkel, M.J.S.T. (author), van Delft, J.H.M. (author), Lohman, P.H.M. (author), Baan, R.A. (author), TNO Voeding (author)

The recent introduction of the phenyl-β-D-galactopyranoside (P-gal)-based positive-selection system for screening of λlacZ phages originating from the λlacZ transgenic mouse (Muta Mouse) has made the determination of mutant frequencies (MF) a much simpler task. Previously, MF data from these mice have been collected by means of the 5-bromo-4...

article 1996

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Relation between benzo[a]pyrene-DNA adducts, cell proliferation and p53 expression in tracheal epithelium of hamsters fed a high B-carotene diet

Wolterbeek, A.P.M. (author), Roggeband, R. (author), Baan, R.A. (author), Feron, V.J. (author), Rutten, A.A.J.J.L. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

Vitamin A and β-carotene protect against respiratory tract cancer by inhibiting the formation of DNA damage and controlling cellular proliferation and differentiation, Recently, it has been shown that the p53 tumor-suppressor gene plays a crucial role in the etiology of respiratory tract cancer. In the present study, we investigated the...

article 1995

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Vitamin A and β-carotene influence the level of benzo[a]pyrene-induced DNA adducts and DNA-repair activities in hamster tracheal epithelium in organ culture

Wolterbeek, A.P.M. (author), Roggeband, R. (author), van Moorsel, C.J.A. (author), Baan, R.A. (author), Koeman, J.H. (author), Feron, V.J. (author), Rutten, A.A.J.J.L. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

Although most studies concerning the effect of vitamin A and β-carotene on chemical carcinogenesis are focused on tumour promotion and progression, these compounds may affect initiation as well. In this study the influence of vitamin A and β-carotene on unscheduled DNA synthesis (UDS) was investigated in hamster tracheal epithelium in organ...

article 1995

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Effect of cigarette-smoke condensate and norharman on the induction of SCEs by direct and indirect mutagens in CHO cells

Rutten, A.A.J.J.L. (author), Wilmer, J.W.G.M. (author), Instituut CIVO-Toxicologie en voeding TNO (author)

article 1986

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Nutritional factors in lung, colon, and prostate carcinogenesis in animal models

Instituut CIVO-Toxicologie en voeding TNO (author), Kroes, R. (author), Beems, R.B. (author), Bosland, M.C. (author), Bunnik, G.S.J. (author), Sinkeldam, E.J. (author)

Dietary factors are now considered to be among the most important environmental risk determinations for cancer. In addition to epidemiological studies, experimental animal studies are an important tool to investigate dietary modulation in carcinogenesis. Results of recent experimental studies on the effect of some nutrients indicate that vitamin...

conference paper 1986