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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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Basil extract inhibits the sulfotransferase mediated formation of DNA adducts of the procarcinogen 1′-hydroxyestragole by rat and human liver S9 homogenates and in HepG2 human hepatoma cells

Jeurissen, S.M.F. (author), Punt, A. (author), Delatour, T. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)

The effects of a basil extract on the sulfation and concomitant DNA adduct formation of the proximate carcinogen 1′-hydroxyestragole were studied using rat and human liver S9 homogenates and the human hepatoma cell line HepG2. Basil was chosen since it contains the procarcinogen estragole that can be metabolized to 1′-hydroxyestragole by...

article 2008

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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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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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Biomonitoring of exposure to chemical warfare agents

TNO Defensie en Veiligheid (author), Noort, D. (author), van der Schans, M.J. (author), Benschop, H.P. (author)

An overview is presented of the major methods that are presently available for biomonitoring of exposure to chemical warfare agents, i.e., nerve agents and sulfur mustard. These methods can be applied for a variety of purposes such as diagnosis and dosimetry of exposure of casualties, verification of nonadherence to the Chemical Weapon...

bookPart 2006

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Formation of transient covalent protein and DNA adducts by quercetin in cells with and without oxidative enzyme activity

TNO Voeding (author), van der Woude, H. (author), Alink, G.M. (author), van Rossum, B.E.J. (author), Walle, K. (author), van Steeg, H. (author), Walle, T. (author), Rietjens, I.M.C.M. (author)

This study investigates the role of cellular tyrosinase and/or peroxidase-like oxidative enzyme activity in the covalent binding of quercetin to glutathione, protein, and DNA, as well as the stability of quercetin DNA adducts in time. This was done by studying the formation of glutathionyl quercetin adducts in various in vitro models, and the...

article 2005

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Biomonitoring of exposure to chemical warfare agents: A review

Noort, D. (author), Benschop, H.P. (author), Black, R.M. (author), Prins Maurits Laboratorium TNO (author)

In this report an overview of the methods currently available for detection of exposure to a number of chemical warfare agents (CWA), i.e., sulfur mustard, lewisite and nerve agents, is presented. Such methods can be applied for various purposes, e.g., diagnosis and dosimetry of exposure of casualties, confirmation of nonexposure, verification...

article 2002

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Biological monitoring the exposure to polycyclic aromatic hydrocarbons of coke oven workers in relation to smoking and genetic polymorphisms for GSTM1 GSTT1

van Delft, J.H.M. (author), Steenwinkel, M.-J.S.T. (author), van Asten, J.G. (author), de Vogel, N. (author), Bruijntjes-Rozier, T.C.D.M. (author), Schouten, T. (author), Cramers, P. (author), Maas, L. (author), van Herwijnen, M.H. (author), van Schooten, F.-J. (author), Hopmans, P.M.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

Occupational exposure to polycyclic aromatic hydrocarbons (PAH) increases the risk of developing lung cancer. Human exposure is often demonstrated by increased internal levels of PAH metabolites and of markers for early biological effects, like DNA adducts and cytogenetic aberrations. Objective: This study aimed to assess whether the current...

article 2001

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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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Cisplatin-DNA adduct formation in rat spermatozoa and its effect on fetal development

Hooser, S.T. (author), van Dijk-Knijnenburg, C.M. (author), Waalkens-Berendsen, I.D.H. (author), Smits-van Prooije, A.E. (author), Snoeij, N.J. (author), Baan, R.A. (author), Fichtinger-Schepman, M.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

Exposure of males to some genotoxic chemicals causes DNA damage in spermatozoa resulting in embryotoxicity and developmental defects in their offspring. This study demonstrates that cisplatin-DNA adducts could be measured in spermatozoa following treatment with the antineoplastic drug, cisplatin. The formation of spermatozoa cisplatin-DNA...

article 2000

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IPCS guidelines for the monitoring of genotoxic effects of carcinogens in humans

Albertini, R.J. (author), Anderson, D. (author), Douglas, G.R. (author), Hagmar, L. (author), Hemminki, K. (author), Merlo, F. (author), Natarajan, A.T. (author), Norppa, H. (author), Shuker, D.E.G. (author), Tice, R. (author), Waters, M.D. (author), Aitio, A. (author), TNO Kwaliteit van Leven TNO Bibra (author)

The purpose of these guidelines is to provide concise guidance on the planning, performing and interpretation of studies to monitor groups or individuals exposed to genotoxic agents. Most human carcinogens are genotoxic but not all genotoxic agents have been shown to be carcinogenic in humans. Although the main interest in these studies is due...

article 2000

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Animal products and K-ras codon 12 and 13 mutations in colon carcinomas

Kampman, E. (author), Voskuil, D.W. (author), van Kraats, A.A. (author), Balder, H.F. (author), van Muijen, G.N.P. (author), Goldbohm, R.A. (author), van 't Veer, P. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

K-ras gene mutations (codons 12 and 13) were determined by PCR-based mutant allele-specific amplification (MASA) in tumour tissue of 185 colon cancer patients: 36% harboured mutations, of which 82% were located in codon 12. High intakes of animal protein, calcium and poultry were differently associated with codon 12 and 13 mutations: odds ratios...

article 2000

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Induction of somatic mutations but not methylated DNA adducts in λlacZ transgenic mice by dichlorvos

Pletsa, V. (author), Steenwinkel, M.-J.S.T. (author), van Delft, J.H.M. (author), Baan, R.A. (author), Kyrtopoulos, S.A. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

In order to examine the in vivo genotoxic activity of dichlorvos, λlacZ transgenic mice (Muta(TM)Mouse) were treated i.p. with single (4.4 or 11 mg/kg) or multiple (5x11 mg/kg) doses of this agent and sacrificed 4 h or 14 days post-treatment for DNA adduct measurement or mutant frequency analysis, respectively. Neither methylated DNA adducts nor...

article 1999

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The potential of platinum-DNA adduct determination in ex vivo treated tumor fragments for the prediction of sensitivity to cisplatin chemotherapy

Welters, M.J.P. (author), Braakhuis, B.J.M. (author), Jacobs-Bergmans, A.J. (author), Kegel, A. (author), Baan, R.A. (author), van der Vijgh, W.J.F. (author), Fichtinger-Schepman, A.M.J. (author), Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding (author)

Background: Response to cisplatin-therapy is assumed to be related to the formation of platinum (Pt)-DNA adducts. Measurement of these adducts prior to therapy could be of value to improve cisplatin based cancer therapy. Materials and methods: We determined Pt-GG and Pt-AG adduct levels by use of 32P-postlabeling after ex vivo cisplatin...

article 1999

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Pharmacodynamics of cisplatin in human head and neck cancer: correlation between platinum content, DNA adduct levels and drug sensitivity in vitro and in vivo

Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding (author), Welters, M.J.P. (author), Fichtinger-Schepman, A.M.J. (author), Baan, R.A. (author), Jacobs-Bergmans, A.J. (author), Kegel, A. (author), van der Vijgh, W.J.F. (author), Braakhuis, B.J.M. (author)

Total platinum contents and cisplatin-DNA adduct levels were determined in vivo in xenografted tumour tissues in mice and in vitro in cultured tumour cells of head and neck squamous cell carcinoma (HNSCC), and correlated with sensitivity to cisplatin. In vivo, a panel of five HNSCC tumour lines growing as xenografts in nude mice was used. In...

article 1999

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Pharmacokinetics of cisplatin with and without amifostine in tumour- bearing nude mice

Korst, A.E.C. (author), Boven, E. (author), van der Sterre, M.L.T. (author), Fichtinger-Schepman, A.M.J. (author), van der Vijgh, W.J.F. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

Amifostine (Ethyol, WR-2721) is in use in the clinic as a protector against platinum-induced toxicities. We have previously reported that amifostine induced a potentiation of the antitumour activity of carboplatin in human ovarian cancer xenografts. An influence of amifostine on the pharmacokinetics of carboplatin, resulting in higher platinum...

article 1998

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Methyl bromide causes DNA methylation in rats and mice but fails to induce somatic mutations in λlacZ transgenic mice

Pletsa, V. (author), Steenwinkel, M.-J.S.T. (author), van Delft, J.H.M. (author), Baan, R.A. (author), Kyrtopoulos, S.A. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

Following single or multiple oral treatments of rats or λlacZ transgenic mice with methyl bromide, methylated DNA adducts (N7- and/or O6-methylguanine) were found at comparable levels in various tissues, including among others the glandular stomach, the forestomach and the liver. Multiple rat treatment resulted in substantial decreases in the...

article 1998

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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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DNA adducts, mutant frequencies and mutation spectra in λlacZ transgenic mice treated with N-nitrosodimethylamine

Souliotis, V.L. (author), van Delft, J.H.M. (author), Steenwinkel, M.-J.S.T. (author), Baan, R.A. (author), Kyrtopoulos, S.A. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

Groups of λlacZ transgenic mice were treated i.p. with N-nitrosodimethylamine (NDMA) as single doses of 5 mg/kg or 10 mg/kg or as 10 daily doses of 1 mg/kg and changes in DNA N7- or O6-methylguanine or the repair enzyme O6-alkylguanine-DNA alkyltransferase (AGT) were followed for up to 14 days in various tissues. Adduct induction in the liver...

article 1998