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Monitoring for DNA damage of humans occupationally exposed to methyl bromide

Pletsa, V. (author), Steenwinkel, M.J.S. (author), Stoikidou, M. (author), van Delft, J.H.M. (author), Baan, R.A. (author), Katsouyanni, K. (author), Kyrtopoulos, S.A. (author), TNO Voeding (author)

article 2002

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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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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)

article 1999

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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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Methyl bromide causes DNA methylation in rats and mice but fails to induce somatic mutations in lambda lacZ trangenic mice

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

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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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

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Biological effect markers for exposure to carcinogenic compound and their relevance for risk assessment

van Delft, J.H.M. (author), Baan, R.A. (author), Roza, L. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

In this review data are summarized on biomarkers that are used for biological effect monitoring of human populations exposed to genotoxic carcinogens. The biomarkers are DNA and protein adducts and cytogenetic effects. Most of these biomarkers are relevant for the process of carcinogenesis. Emphasis is on providing information on the properties...

article 1998

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DNA adducts, mutant frequencies, and mutation spectra in various organs of λlacZ mice exposed to ethylating agents

Mientjes, E.J. (author), Luiten-Schuite, A. (author), van der Wolf, E. (author), Borsboom, Y. (author), Bergmans, A. (author), Berends, F. (author), Lohman, P.H.M. (author), Baan, R.A. (author), van Delft, J.H.M. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

To investigate tissue-specific relations between DNA adducts and mutagenesis in vivo, λlacZ transgenic mice were treated i.p. with N-ethyl-N-nitrosourea (ENU), diethylnitrosamine (DEN), and ethyl methanesulphonate (EMS). In liver, bone marrow, and brain DNA from mice sacrificed at several time points after treatment O6-ethylguanine (O6-EtG) and...

article 1998

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Gene-mutation assays in lambda-lacZ transgenic mice: Comparison of lacZ with endogenous genes in splenocytes and small intestinal epithelium

van Delft, J.H.M. (author), Bergmans, A. (author), van Dam, F.J. (author), Tates, A.D. (author), Howard, L. (author), Winton, D.J. (author), Baan, R.A. (author)

Comparison of results derived from transgenic animal gene-mutation assays with those from mutation analyses in endogenous genes is an important step in the validation of the former. We have used λlacZ transgenic mice to study alkylation-induced mutagenesis in vivo in (a) lacZ and hprt in spleen cells, and (b) lacZ and Dlb-1 in small intestine...

article 1998

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Influence of nucleotide excision repair on N-hydroxy-2-acetylaminofluorene-induced mutagenesis studied in λlacZ-transgenic mice

Frijhoff, A.F.W. (author), Krul, C.A.M. (author), de Vries, A. (author), Kelders, M.C.J.M. (author), Weeda, G. (author), van Steeg, H. (author), Baan, R.A. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

To study the influence of nucleotide excision repair (NER) on mutagenesis in vivo, ERCC1+/-, XPA-/-, and wild-type (ERCC1+/+ and XPA+/+, respectively) λlacZ-transgenic mice were treated i.p. with N-hydroxy-2-acetylaminofluorene (N-OH-AAF) and lacZ mutant frequencies were determined in liver. No significant effect of the treatment on the mutant...

article 1998

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UVB-induced mutations in the skin of hairless transgenic mice

Frijhoff, A.F.W. (author), Rebel, H.G. (author), Steenwinkel, M.J.S.T. (author), van Delft, J.H.M. (author), Baan, R.A. (author), Roza, L. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

conference paper 1998

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The formation and repair of cisplatin-DNA adducts in wild-type and cisplatin-resistant L1210 cells: Comparison of immunocytochemical determination with detection in isolated DNA

Blommaert, F.A. (author), Floot, B.G.J. (author), van Dijk-Knijnenburg, H.C.M. (author), Berends, F. (author), Baan, R.A. (author), Schornagel, J.H. (author), den Engelse, L. (author), Fichtinger-Schepman, A.M.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

We have studied the formation and repair of cisplatin-DNA adducts in wild-type mouse leukemia L1210/0 cells and in the sublines L1210/2 and L1210/5, which differ in cisplatin sensitivity. In a colony-formation assay these sublines were 9- and 22-fold more resistant compared to L1210/0, respectively. Cisplatin-induced DNA modification was studied...

article 1998

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Role of glutathione, glutathione S-transferases and multidrug resistance-related proteins in cisplatin sensitivity of head and neck cancer cell lines

Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding (author), Welters, M.J.P. (author), Fichtinger-Schepman, A.M.J. (author), Baan, R.A. (author), Flens, M.J. (author), Scheper, R.J. (author), Braakhuis, B.J.M. (author)

Resistance to chemotherapy is a major problem in the treatment of patients with head and neck squamous cell carcinoma (HNSCC). Important factors involved are drug detoxification by glutathione (GSH) and reduced drug accumulation due to active transport out of the cell by so-called 'multidrug resistance-related proteins'. We have studied a panel...

article 1998

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Production of a congenic mouse strain carrying the hairless (hr) mutation in a 129/Ola genetic background: A suitable strain to generate transgenic and knockout mice for studies on toxicity and carcinogenesis of skin

Frijhoff, A.F.W. (author), Bol, S.A.M. (author), Groot, P.C. (author), van Zeeland, A.A. (author), Demant, P. (author), Baan, R.A. (author), TNO voeding (author)

article 1996

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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