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1. New insights into the mechanisms underlying 5-fluorouracil-induced intestinal toxicity based on transcriptomic and metabolomic responses in human intestinal organoids

Author

Rodrigues, Daniela, de Souza, Terezinha, Coyle, Luke, Di Piazza, Matteo, Herpers, Bram, Ferreira, Sofia, Zhang, Mian, Vappiani, Johanna, Sévin, Daniel C., Gabor, Attila, Lynch, Anthony, Chung, Seung-Wook, Saez-Rodriguez, Julio, Jennen, Danyel G. J., Kleinjans, Jos C. S., and de Kok, Theo M.

Published
2021
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3. Correction to: Toxicogenomics directory of chemically exposed human hepatocytes

Author

Grinberg, Marianna, Stöber, Regina M., Edlund, Karolina, Rempel, Eugen, Godoy, Patricio, Reif, Raymond, Widera, Agata, Madjar, Katrin, Schmidt-Heck, Wolfgang, Marchan, Rosemarie, Sachinidis, Agapios, Spitkovsky, Dimitry, Hescheler, Jürgen, Carmo, Helena, Arbo, Marcelo D., van de Water, Bob, Wink, Steven, Vinken, Mathieu, Rogiers, Vera, Escher, Sylvia, Hardy, Barry, Mitic, Dragana, Apic, Gordana, Myatt, Glenn, Waldmann, Tanja, Mardinoglu, Adil, Damm, Georg, Seehofer, Daniel, Nüssler, Andreas, Weiss, Thomas S., Oberemm, Axel, Lampen, ·Alfons, Schaap, Mirjam M., Luijten, Mirjam, van Steeg, Harry, Thasler, Wolfgang E., Kleinjans, Jos C. S., Stierum, Rob H., Leist, ·Marcel, Rahnenführer, Jörg, and Hengstler, Jan G.

Published
2022
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4. Associations Between Genome-wide Gene Expression and Ambient Nitrogen Oxides

Author

Mostafavi, Nahid, Vlaanderen, Jelle, Portengen, Lutzen, Chadeau-Hyam, Marc, Modig, Lars, Palli, Domenico, Bergdahl, Ingvar A., Brunekreef, Bert, Vineis, Paolo, Hebels, Dennie G. A. J., Kleinjans, Jos C. S., Krogh, Vittorio, Hoek, Gerard, Georgiadis, Panagiotis, Kyrtopoulos, Soterios A., and Vermeulen, Roel

Published
2017

6. Epigenome-wide association study of adiposity and future risk of obesity-related diseases

Author

Campanella, Gianluca, Gunter, Marc J., Polidoro, Silvia, Krogh, Vittorio, Palli, Domenico, Panico, Salvatore, Sacerdote, Carlotta, Tumino, Rosario, Fiorito, Giovanni, Guarrera, Simonetta, Iacoviello, Licia, Bergdahl, Ingvar A., Melin, Beatrice, Lenner, Per, de Kok, Theo M. C. M., Georgiadis, Panagiotis, Kleinjans, Jos C. S., Kyrtopoulos, Soterios A., Bueno-de-Mesquita, H. Bas, Lillycrop, Karen A., May, Anne M., Onland-Moret, N. Charlotte, Murray, Robert, Riboli, Elio, Verschuren, Monique, Lund, Eiliv, Mode, Nicolle, Sandanger, Torkjel M., Fiano, Valentina, Trevisan, Morena, Matullo, Giuseppe, Froguel, Philippe, Elliott, Paul, Vineis, Paolo, and Chadeau-Hyam, Marc

Published
2018
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11. “Watching the Detectives” report of the general assembly of the EU project DETECTIVE Brussels, 24–25 November 2015

Author

Fernando, Ruani N., Chaudhari, Umesh, Escher, Sylvia E., Hengstler, Jan G., Hescheler, Jürgen, Jennings, Paul, Keun, Hector C., Kleinjans, Jos C. S., Kolde, Raivo, Kollipara, Laxmikanth, Kopp-Schneider, Annette, Limonciel, Alice, Nemade, Harshal, Nguemo, Filomain, Peterson, Hedi, Prieto, Pilar, Rodrigues, Robim M., Sachinidis, Agapios, Schäfer, Christoph, Sickmann, Albert, Spitkovsky, Dimitry, Stöber, Regina, van Breda, Simone G. J., van de Water, Bob, Vivier, Manon, Zahedi, René P., Vinken, Mathieu, and Rogiers, Vera

Published
2016
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13. Toxicogenomics directory of chemically exposed human hepatocytes (vol 88, pg 2261, 2014)

Author

Grinberg, Marianna, Stoeber, Regina M., Edlund, Karolina, Rempel, Eugen, Godoy, Patricio, Reif, Raymond, Widera, Agata, Madjar, Katrin, Schmidt-Heck, Wolfgang, Marchan, Rosemarie, Sachinidis, Agapios, Spitkovsky, Dimitry, Hescheler, Juergen, Carmo, Helena, Arbo, Marcelo D., van de Water, Bob, Wink, Steven, Vinken, Mathieu, Rogiers, Vera, Escher, Sylvia, Hardy, Barry, Mitic, Dragana, Apic, Gordana, Myatt, Glenn, Waldmann, Tanja, Mardinoglu, Adil, Damm, Georg, Seehofer, Daniel, Nuessler, Andreas, Weiss, Thomas S., Oberemm, Axel, Lampen, Alfons, Schaap, Mirjam M., Luijten, Mirjam, van Steeg, Harry, Thasler, Wolfgang E., Kleinjans, Jos C. S., Stierum, Rob H., Leist, Marcel, Rahnenfuehrer, Joerg, Hengstler, Jan G., Grinberg, Marianna, Stoeber, Regina M., Edlund, Karolina, Rempel, Eugen, Godoy, Patricio, Reif, Raymond, Widera, Agata, Madjar, Katrin, Schmidt-Heck, Wolfgang, Marchan, Rosemarie, Sachinidis, Agapios, Spitkovsky, Dimitry, Hescheler, Juergen, Carmo, Helena, Arbo, Marcelo D., van de Water, Bob, Wink, Steven, Vinken, Mathieu, Rogiers, Vera, Escher, Sylvia, Hardy, Barry, Mitic, Dragana, Apic, Gordana, Myatt, Glenn, Waldmann, Tanja, Mardinoglu, Adil, Damm, Georg, Seehofer, Daniel, Nuessler, Andreas, Weiss, Thomas S., Oberemm, Axel, Lampen, Alfons, Schaap, Mirjam M., Luijten, Mirjam, van Steeg, Harry, Thasler, Wolfgang E., Kleinjans, Jos C. S., Stierum, Rob H., Leist, Marcel, Rahnenfuehrer, Joerg, and Hengstler, Jan G.

Published
2022

15. Evaluation of Adverse Effects of Resorbable Hyaluronic Acid Fillers: Determination of Macrophage Responses

Author

De Jong, Wim H., primary, Jennen, Danyel, additional, Keizers, Peter H. J., additional, Hodemaekers, Hennie M., additional, Vermeulen, Jolanda P., additional, Bakker, Frank, additional, Schwillens, Paul, additional, van Herwijnen, Marcel, additional, Jetten, Marlon, additional, Kleinjans, Jos C. S., additional, Geertsma, Robert E., additional, and Vandebriel, Rob J., additional

Published
2022
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21. Toxicogenomics directory of chemically exposed human hepatocytes

Author

Grinberg, Marianna, Stöber, Regina M., Edlund, Karolina, Rempel, Eugen, Godoy, Patricio, Reif, Raymond, Widera, Agata, Madjar, Katrin, Schmidt-Heck, Wolfgang, Marchan, Rosemarie, Sachinidis, Agapios, Spitkovsky, Dimitry, Hescheler, Jürgen, Carmo, Helena, Arbo, Marcelo D., van de Water, Bob, Wink, Steven, Vinken, Mathieu, Rogiers, Vera, Escher, Sylvia, Hardy, Barry, Mitic, Dragana, Myatt, Glenn, Waldmann, Tanja, Mardinoglu, Adil, Damm, Georg, Seehofer, Daniel, Nüssler, Andreas, Weiss, Thomas S., Oberemm, Axel, Lampen, Alfons, Schaap, Mirjam M., Luijten, Mirjam, van Steeg, Harry, Thasler, Wolfgang E., Kleinjans, Jos C. S., Stierum, Rob H., Leist, Marcel, Rahnenführer, Jörg, and Hengstler, Jan G.

Published
2014
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38. Pre-diagnostic blood immune markers, incidence and progression of B-cell lymphoma and multiple myeloma: Univariate and functionally informed multivariate analyses

Author

Vermeulen, Roel, Saberi Hosnijeh, Fatemeh, Bodinier, Barbara, Portengen, Lützen, Liquet, Benoît, Garrido-Manriquez, Javiera, Lokhorst, Henk, Bergdahl, Ingvar A, Kyrtopoulos, Soterios A, Johansson, Ann-Sofie, Georgiadis, Panagiotis, Melin, Beatrice, Palli, Domenico, Krogh, Vittorio, Panico, Salvatore, Sacerdote, Carlotta, Tumino, Rosario, Vineis, Paolo, Castagné, Raphaële, Chadeau-Hyam, Marc, Botsivali, Maria, Chatziioannou, Aristotelis, Valavanis, Ioannis, Kleinjans, Jos C S, de Kok, Theo M C M, Keun, Hector C, Athersuch, Toby J, Kelly, Rachel, Lenner, Per, Hallmans, Göran, Stephanou, Euripides G, Myridakis, Antonis, Kogevinas, Manolis, Fazzo, Lucia, De Santis, Marco, Comba, Pietro, Bendinelli, Benedetta, Kiviranta, Hannu, Rantakokko, Panu, Airaksinen, Riikka, Ruokojarvi, Paivi, Gilthorpe, Mark, Fleming, Sarah, Fleming, Thomas, Tu, Yu-Kang, Lundh, Thomas, Chien, Kuo-Liong, Chen, Wei J, Lee, Wen-Chung, Kate Hsiao, Chuhsing, Kuo, Po-Hsiu, Hung, Hung, Liao, Shu-Fen, Vermeulen, Roel, Saberi Hosnijeh, Fatemeh, Bodinier, Barbara, Portengen, Lützen, Liquet, Benoît, Garrido-Manriquez, Javiera, Lokhorst, Henk, Bergdahl, Ingvar A, Kyrtopoulos, Soterios A, Johansson, Ann-Sofie, Georgiadis, Panagioti, Melin, Beatrice, Palli, Domenico, Krogh, Vittorio, Panico, Salvatore, Sacerdote, Carlotta, Tumino, Rosario, Vineis, Paolo, Castagné, Raphaële, Chadeau-Hyam, Marc, Botsivali, Maria, Chatziioannou, Aristoteli, Valavanis, Ioanni, Kleinjans, Jos C S, de Kok, Theo M C M, Keun, Hector C, Athersuch, Toby J, Kelly, Rachel, Lenner, Per, Hallmans, Goran, Stephanou, Euripides G, Myridakis, Antoni, Kogevinas, Manoli, Fazzo, Lucia, De Santis, Marco, Comba, Pietro, Bendinelli, Benedetta, Kiviranta, Hannu, Rantakokko, Panu, Airaksinen, Riikka, Ruokojarvi, Paivi, Gilthorpe, Mark, Fleming, Sarah, Fleming, Thoma, Tu, Yu-Kang, Lundh, Thoma, Chien, Kuo-Liong, Chen, Wei J, Lee, Wen-Chung, Kate Hsiao, Chuhsing, Kuo, Po-Hsiu, Hung, Hung, Liao, Shu-Fen, One Health Chemisch, dIRAS RA-2, Sub Physical Oceanography, and Immunology

Subjects
Adult, Male, Vascular Endothelial Growth Factor A, multivariate model, prospective cohort, lymphoma, multivariate models, cytokine, Humans, Prospective Studies, Chemokine CCL7, Aged, Cancer och onkologi, mixed-effect modeling, Chemokine CX3CL1, Incidence, mixed‐effect modeling, Middle Aged, Transforming Growth Factor alpha, Prognosis, time to diagnosis, Europe, multiple myeloma, Case-Control Studies, Cancer and Oncology, Multivariate Analysis, Female, Fibroblast Growth Factor 2, Lymphoma, Large B-Cell, Diffuse, Biomarkers, Cancer Epidemiology, Follow-Up Studies
Abstract

Recent prospective studies have shown that dysregulation of the immune system may precede the development of B‐cell lymphomas (BCL) in immunocompetent individuals. However, to date, the studies were restricted to a few immune markers, which were considered separately. Using a nested case–control study within two European prospective cohorts, we measured plasma levels of 28 immune markers in samples collected a median of 6 years before diagnosis (range 2.01–15.97) in 268 incident cases of BCL (including multiple myeloma [MM]) and matched controls. Linear mixed models and partial least square analyses were used to analyze the association between levels of immune marker and the incidence of BCL and its main histological subtypes and to investigate potential biomarkers predictive of the time to diagnosis. Linear mixed model analyses identified associations linking lower levels of fibroblast growth factor‐2 (FGF‐2 p = 7.2 × 10−4) and transforming growth factor alpha (TGF‐α, p = 6.5 × 10−5) and BCL incidence. Analyses stratified by histological subtypes identified inverse associations for MM subtype including FGF‐2 (p = 7.8 × 10−7), TGF‐α (p = 4.08 × 10−5), fractalkine (p = 1.12 × 10−3), monocyte chemotactic protein‐3 (p = 1.36 × 10−4), macrophage inflammatory protein 1‐alpha (p = 4.6 × 10−4) and vascular endothelial growth factor (p = 4.23 × 10−5). Our results also provided marginal support for already reported associations between chemokines and diffuse large BCL (DLBCL) and cytokines and chronic lymphocytic leukemia (CLL). Case‐only analyses showed that Granulocyte‐macrophage colony stimulating factor levels were consistently higher closer to diagnosis, which provides further evidence of its role in tumor progression. In conclusion, our study suggests a role of growth‐factors in the incidence of MM and of chemokine and cytokine regulation in DLBCL and CLL., What's new? B‐cell lymphomas (BCL) are frequent in immunocompromised individuals, but most BCL cases are thought to occur as a consequence of minor immune perturbations in otherwise immunocompetent individuals. Here the authors prospectively examined a panel of immune markers in the blood from 268 patients afflicted with BCL and paired controls. The data uncover a functional role for growth factors (i.e. FGF‐2, TGF‐alpha) in the incidence and progression of multiple myeloma, a BCL subtype, and underscore the importance of chemokine and cytokine regulation in diffuse large B‐cell lymphoma and chronic lymphocytic leukemia.

Published
2018

43. DNA methylation profiling implicates exposure to PCBs in the pathogenesis of B-cell chronic lymphocytic leukemia

Author

Georgiadis, Panagiotis, Gavriil, Marios, Rantakokko, Panu, Ladoukakis, Efthymios, Botsivali, Maria, Kelly, Rachel S., Bergdahl, Ingvar A., Kiviranta, Hannu, Vermeulen, Roel C. H., Spaeth, Florentin, Hebbels, Dennie G. A. J., Kleinjans, Jos C. S., de Kok, Theo M. C. M., Palli, Domenico, Vineis, Paolo, Kyrtopoulos, Soterios A., Gottschalk, Ralph, van Leeuwen, Danitsja, Timmermans, Leen, Bendinelli, Benedetta, Portengen, Lutzen, Saberi-Hosnijeh, Fatemeh, Melin, Beatrice, Hallmans, Goran, Lenner, Per, Keun, Hector C., Siskos, Alexandros, Athersuch, Toby J., Kogevinas, Manolis, Stephanou, Euripides G., Myridakis, Antonis, Fazzo, Lucia, De Santis, Marco, Comba, Pietro, Airaksinen, Riikka, Ruokojarvi, Paivi, Gilthorpe, Mark, Fleming, Sarah, Fleming, Thomas, Tu, Yu-Kang, Jonsson, Bo, Lundh, Thomas, Chen, Wei J., Lee, Wen-Chung, Hsiao, Chuhsing Kate, Chien, Kuo-Liong, Kuo, Po-Hsiu, Hung, Hung, Liao, Shu-Fen, Toxicogenomics, RS: GROW - R1 - Prevention, RS: FSE MaCSBio, RS: FPN MaCSBio, RS: FHML MaCSBio, RS: MHeNs - R3 - Neuroscience, and Commission of the European Communities

Subjects
Male, EnviroGenomarkers consortium, HYPOMETHYLATION, 010501 environmental sciences, medicine.disease_cause, 01 natural sciences, Pathogenesis, Blood plasma, LYMPHOMA, skin and connective tissue diseases, lcsh:Environmental sciences, General Environmental Science, lcsh:GE1-350, RISK, 0303 health sciences, DNA methylation, ROLES, B-cell lymphoma, Melanoma, Persistent organic pollutants, Middle Aged, Polychlorinated Biphenyls, CANCER, 3. Good health, Italy, Molecular epidemiology, Female, Stem cell, Adult, GENES, POLYCOMB, Article, 03 medical and health sciences, Arbetsmedicin och miljömedicin, MD Multidisciplinary, medicine, Humans, Environmental toxicology, Gene, 030304 developmental biology, 0105 earth and related environmental sciences, Sweden, POLYCHLORINATED BIPHENYL EXPOSURES, Occupational Health and Environmental Health, medicine.disease, HYPERMETHYLATION, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, 13. Climate action, Cancer research, sense organs, Carcinogenesis, Hazard assessment, Environmental Sciences
Abstract

Objectives: To characterize the impact of PCB exposure on DNA methylation in peripheral blood leucocytes and to evaluate the corresponding changes in relation to possible health effects, with a focus on B-cell lymphoma. Methods: We conducted an epigenome-wide association study on 611 adults free of diagnosed disease, living in Italy and Sweden, in whom we also measured plasma concentrations of 6 PCB congeners, DDE and hexachlorobenzene. Results: We identified 650 CpG sites whose methylation correlates strongly (FDR

Published
2019

45. Acetaminophen Overdose as a Potential Risk Factor for Parkinson's Disease

Author

Bohler, Sacha, Bohler, Sacha, Liu, Xiaosong, Krauskopf, Julian, Gaiment, Florian, Aubrecht, Jiri, Nicolaes, Gerry A. F., Kleinjans, Jos C. S., Briede, Jacco J., Bohler, Sacha, Bohler, Sacha, Liu, Xiaosong, Krauskopf, Julian, Gaiment, Florian, Aubrecht, Jiri, Nicolaes, Gerry A. F., Kleinjans, Jos C. S., and Briede, Jacco J.

Abstract

Four complementary approaches were used to investigate acetaminophen overdose as a risk factor for Parkinson's disease (PD). Circulating microRNAs (miRNAs) serum profiles from acetaminophen-overdosed patients were compared with patients with terminal PD, revealing four shared miRNAs. Similarities were found among molecular structures of dopamine (DA), acetaminophen, and two known PD inducers indicating affinity for dopaminergic transport. Potential interactions between acetaminophen and the human DA transporter were confirmed by molecular docking modeling and binding free energy calculations. Thus, it is plausible that acetaminophen is taken up by the dopaminergic transport system into the substantia nigra (SN). A ChEMBL query identified proteins that are similarly targeted by DA and acetaminophen. Here, we highlight CYP3A4, present in the SN, a predominant metabolizer of acetaminophen into its toxic metabolite N-acetyl-p-benzoquinone imine and shown to be regulated in PD. Overall, based on our results, we hypothesize that overdosing of acetaminophen is a potential risk factor for parkinsonism.

Published
2019

50. Persistence of Epigenomic Effects After Recovery From Repeated Treatment With Two Nephrocarcinogens

Author

Limonciel, Alice, van Breda, Simone G., Jiang, Xiaoqi, Tredwell, Gregory D., Wilmes, Anja, Aschauer, Lydia, Siskos, Alexandros P., Sachinidis, Agapios, Keun, Hector C., Kopp-Schneider, Annette, de Kok, Theo M., Kleinjans, Jos C. S., Jennings, Paul, Limonciel, Alice, van Breda, Simone G., Jiang, Xiaoqi, Tredwell, Gregory D., Wilmes, Anja, Aschauer, Lydia, Siskos, Alexandros P., Sachinidis, Agapios, Keun, Hector C., Kopp-Schneider, Annette, de Kok, Theo M., Kleinjans, Jos C. S., and Jennings, Paul

Abstract

The discovery of the epigenetic regulation of transcription has provided a new source of mechanistic understanding to long lasting effects of chemicals. However, this information is still seldom exploited in a toxicological context and studies of chemical effect after washout remain rare. Here we studied the effects of two nephrocarcinogens on the human proximal tubule cell line RPTEC/TERT1 using high-content mRNA microarrays coupled with miRNA, histone acetylation (HA) and DNA methylation (DM) arrays and metabolomics during a 5-day repeat-dose exposure and 3 days after washout. The mycotoxin ochratoxin A (OTA) was chosen as a model compound for its known impact on HA and DM. The foremost effect observed was the modulation of thousands of mRNAs and histones by OTA during and after exposure. In comparison, the oxidant potassium bromate (KBrO3) had a milder impact on gene expression and epigenetics. However, there was no strong correlation between epigenetic modifications and mRNA changes with OTA while with KBrO3 the gene expression data correlated better with HA for both up-and down-regulated genes. Even when focusing on the genes with persistent epigenetic modifications after washout, only half were coupled to matching changes in gene expression induced by OTA, suggesting that while OTA causes a major effect on the two epigenetic mechanisms studied, these alone cannot explain its impact on gene expression. Mechanistic analysis confirmed the known activation of Nrf2 and p53 by KBrO3, while OTA inhibited most of the same genes, and genes involved in the unfolded protein response. A few miRNAs could be linked to these effects of OTA, albeit without clear contribution of epigenetics to the modulation of the pathways at large. Metabolomics revealed disturbances in amino acid balance, energy catabolism, nucleotide metabolism and polyamine metabolism with both chemicals. In conclusion, the large impact of OTA on transcription was confirmed at the mRNA level but also with

Published
2018

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