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Automated Network Assembly of Mechanistic Literature for Informed Evidence Identification to Support Cancer Risk Assessment

Krishnan, S. (author), Vermeulen, R. (author), Pronk, A. (author), Gyori, B.M. (author), Bachman, J.A. (author), Vlaanderen, J. (author), Stierum, R. (author)

BACKGROUND: Mechanistic data is increasingly used in hazard identification of chemicals. However, the volume of data is large, challenging the efficient identification and clustering of relevant data. OBJECTIVES: We investigated whether evidence identification for hazard assessment can become more efficient and informed through an automated...

article 2022

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Changes in DNA methylation induced by multi-walled carbon nanotube exposure in the workplace

Ghosh, M (author), Oner, D. (author), Poels, K. (author), Tabish, A.M. (author), Vlaanderen, J. (author), Pronk, A. (author), Kuijpers, E. (author), Lan, Q. (author), Vermeulen, R. (author), Bekaert, B. (author), Hoet, P.H.M. (author), Godderis, L. (author)

This study was designed to assess the epigenetic alterations in blood cells, induced by occupational exposure to multi-wall carbon nanotubes (MWCNT). The study population comprised of MWCNT-exposed workers (n=24) and unexposed controls (n=43) from the same workplace. We measured global DNA methylation/hydroxymethylation levels on the 5th...

article 2017

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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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Analysis of temporal gene expression during Bacillus subtilis spore germination and outgrowth

Keijser, B.J.F. (author), ter Beek, A. (author), Rauwerda, H. (author), Schuren, F. (author), Montijn, R. (author), van der Spek, H. (author), Brul, S. (author), TNO Kwaliteit van Leven (author)

Bacillus subtilis forms dormant spores upon nutrient depletion. Under favorable environmental conditions, the spore breaks its dormancy and resumes growth in a process called spore germination and outgrowth. To elucidate the physiological processes that occur during the transition of the dormant spore to an actively growing vegetative cell, we...

article 2007

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Meat and fish consumption, APC gene mutations and hMLH1 expression in colon and rectal cancer: A prospective cohort study (The Netherlands)

Lüchtenborg, M. (author), Weijenberg, M.P. (author), de Goeij, A.F.P.M. (author), Wark, P.A. (author), Brink, M. (author), Roemen, G.M.J.M. (author), Lentjes, M.H.F.M. (author), de Bruïne, A.P. (author), Goldbohm, R.A. (author), van 't Veer, P. (author), van den Brandt, P.A. (author), TNO Kwaliteit van Leven TNO Voeding (author)

Objective: The aim of this study was to investigate the associations between meat and fish consumption and APC mutation status and hMLH1 expression in colon and rectal cancer. Methods: The associations were investigated in the Netherlands Cohort Study, and included 434 colon and 154 rectal cancer patients on whom case-cohort analyses (subcohort...

article 2005

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Evaluation of the Xpa-Deficient Transgenic Mouse Model for Short-Term Carcinogenicity Testing: 9-Month Studies with Haloperidol, Reserpine, Phenacetin, and D-Mannitol

Lina, B.A.R. (author), Woutersen, R.A. (author), Bruijntjes, J.P. (author), van Benthem, J. (author), van den Berg, J.A.H. (author), Monbaliu, J. (author), Thoolen, B.J.J.M. (author), Beems, R.B. (author), van Kreijl, C.F. (author), TNO Voeding (author)

As part of the international evaluation program coordinated by ILSI/HESI, the potential of DNA repair deficient Xpa-/- mice and the double knockout Xpa-/-.p53+/- mice for short term carcinogenicity assays was evaluated. For comparison also wild-type C57BL/6 mice (WT) were included in these studies. Four test compounds were administered to groups...

article 2004

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Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

van Erk, M.J. (author), Teuling, E. (author), Staal, Y.C.M. (author), Huybers, S. (author), van Bladeren, P.J. (author), Aarts, J.M.M.J.G. (author), van Ommen, B. (author), TNO Voeding (author)

Background. Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an anti-oxidant and it can act as an anti...

article 2004

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Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in humans. An assessment of early genotoxic markers

Rhodes, L.E. (author), Shahbakhti, H. (author), Azurdia, R.M. (author), Moison, R.M.W. (author), Steenwinkel, M.J.S.T. (author), Homburg, M.I. (author), Dean, M.P. (author), McArdle, F. (author), Beijersbergen van Henegouwen, G.M.J. (author), Epe, B. (author), Vink, A.A. (author)

Dietary omega-3 polyunsaturated fatty acids (ω-3 PUFAs) protect against photocarcinogenesis in animals, but prospective human studies are scarce. The mechanism(s) underlying the photoprotection are uncertain, although ω-3 PUFAs may influence oxidative stress. We examined the effect of supplementation on a range of indicators of ultraviolet...

article 2003

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Detection of single-strand breaks and base damage in DNA of human white blood cells as a tool for biological dosimetry of exposure to ionizing radiation

van der Schans, G.P. (author), Timmerman, A.J. (author), Bruijnzeel, P.L.B. (author)

An immunochemical assay has been adapted to detect DNA damage in whole blood at biologically relevant doses of ionizing radiation. Upon alkaline treatment of whole blood, both strand breaks and base damage (which is converted into strand breaks by the addition of damage-specific enzymes) are detected by using antibodies that specifically bind to...

article 2002

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Melanin offers protection against induction of cyclobutane pyrimidine dimers and 6-4 photoproducts by UVB in cultured human melanocytes

Smit, N.P.M. (author), Vink, A.A. (author), Kolb, R.M. (author), Steenwinkel, M.J.S.T. (author), van den Berg, P.T.M. (author), van Nieuwpoort, F. (author), Roza, L. (author), Pavel, S. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

The goal of this investigation was to correlate the melanin content in human pigmentary cells with the generation of UVB-induced photoproducts and to examine the relationship between the melanin content and the removal of the photoproducts. Cultured melanocytes from light-skinned individuals synthesized less melanin and produced more cyclobutane...

article 2001

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UV-induced DNA incision and proliferating cell nuclear antigen recruitment to repair sites occur independently of p53-replication protein A interaction in p53 wild type and mutant ovarian carcinoma cells

Riva, F. (author), Zuco, V. (author), Vink, A.A. (author), Supino, R. (author), Prosperi, E. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

The tumour suppressor gene TP53 plays an important role in the regulation of DNA repair, and particularly of nucleotide excision repair. The influence of p53 status on the efficiency of the principal steps of this repair pathway was investigated after UV-C irradiation in the human ovarian carcinoma cell line IGROV-1 (expressing wild-type p53)...

article 2001

document

An immunochemical assay to detect DNA damage in bovine sperm

van der Schans, G.P. (author), Haring, R. (author), van Dijk- Knijnenburg, H.C.M. (author), Bruijnzeel, P.L.B. (author), den Daas, N.H.G. (author)

An immunochemical assay has been developed to detect oxidative damage in bovine sperm DNA. Sperm DNA contains a large amount of oxidative damage as a result of exposure to exogenous agents, but damage also can caused by normal metabolic processes and the absence of DNA repair in the later stages of spermatogenesis. A freeze-thaw procedure...

article 2000

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Lack of effect of coumarin on unscheduled DNA synthesis in the in vivo rat hepatocyte DNA repair assay

Edwards, A.J. (author), Price, R.J. (author), Renwick, A.B. (author), Lake, B.G. (author), TNO BIBRA TNO Kwaliteit van Leven (author)

The ability of coumarin to induce UDS in male Sprague-Dawley CD rat hepatocytes in vivo was assessed using the unscheduled DNA synthesis (UDS) assay. From a preliminary toxicity study the oral maximum tolerated dose (MTD) of coumarin was determined to be 320mg/kg body weight. For the UDS studies, rats were treated with 0 (corn oil control), 32 ...

article 2000

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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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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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Formation and persistence of O6-ethylguanine in genomic and transgene DNA in liver and brain of λlacZ transgenic mice treated with N-ethyl-N-nitrosourea

Mientjes, E.J. (author), Hochleitner, K. (author), Luiten-Schuite, A. (author), van Delft, J.H.M. (author), Thomale, J. (author), Berends, F. (author), Rajewsky, M.F. (author), Lohman, P.H.M. (author), Baan, R.A. (author), TNO Voeding (author)

LacZ transgenic mice are suitable for short-term mutagenicity studies in vivo. Mutagenicity in these mice is determined in the lacZ transgene. Since the lacZ gene is of bacterial origin the question has been raised whether DNA-adduct formation and repair in the transgene are comparable to those in total genomic DNA. Mice were treated with N...

article 1996

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Methyl DNA adducts, DNA repair, and hypoxanthine-guanine phosphoribosyl transferase mutations in peripheral white blood cells from patients with malignant melanoma treated with dacarbazine and hydroxyurea

Philip, P.A. (author), Souliotis, V.L. (author), Harris, A.L. (author), Salisbury, A. (author), Tates, A.D. (author), Mitchell, K. (author), van Delft, J.H.M. (author), Ganesan, T.S. (author), Kyrtopoulos, S.A. (author), TNO Voeding (author)

Dacarbazine (DTIC) is a DNA-methylating drug used in the treatment of malignant melanoma. Among the DNA dducts induced by DTIC are N7-methylguanine (N7-meG) and O6-methylguamne (O6-meG). The latter adduct, in particular, may be important in the mutagenic as well as the cytotoxic activity of DTIC. Repair of O6-meG is carried out by the enzyme O6...

article 1996

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The role of DNA damage and repair in ultraviolet B radiation-induced immunomodulation: Relevance for human photocarcinogenesis

TNO Nutrition and Food Research (author), Krutmann, J. (author), Ahrens, C. (author), Roza, L. (author), Arlett, C.F. (author)

Chemicals/CAS: Intercellular Adhesion Molecule-1, 126547-89-5; Pyrimidine Dimers

article 1996

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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