DOCSLIB.ORG

Towards Next Generation Risk Assessment of Chemicals: Bayesian

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Towards Next Generation Risk Assessment of Chemicals: Bayesian Towards next generation risk assessment of chemicals : bayesian meta-analysis of human variability in metabolism and transporters and application for the derivation of pathway-related uncertainty factors Keyvin Darney To cite this version: Keyvin Darney. Towards next generation risk assessment of chemicals : bayesian meta-analysis of human variability in metabolism and transporters and application for the derivation of pathway- related uncertainty factors. Toxicology. Université de Bretagne occidentale - Brest, 2020. English. NNT : 2020BRES0013. tel-03227086 HAL Id: tel-03227086 https://tel.archives-ouvertes.fr/tel-03227086 Submitted on 16 May 2021 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. THESE DE DOCTORAT DE L'UNIVERSITE DE BRETAGNE OCCIDENTALE ECOLE DOCTORALE N° 605 Biologie Santé Spécialité : Toxicologie Par Keyvin DARNEY Towards next generation risk assessment of chemicals: Bayesian meta-analysis of Human variability in metabolism and transporters and application for the derivation of pathway-related uncertainty factors Thèse présentée et soutenue à Maisons-Alfort, le 26 février 2020 Unité de recherche : Unité Méthodologies et Etudes, Direction d’Evaluation des Risques - Anses Rapporteurs avant soutenance : Sami HADDAD Professeur titulaire, Faculté de médecine, Université de Montréal Michel LAURENTIE Chef d’unité Expérimentation, Modélisation et Analyse de Données, Anses Composition du Jury : Président : Xavier DECLEVES Professeur des universités-praticien hospitalier, Université Paris Descartes Examinateurs : Laurent BODIN Ingénieur-chercheur, CEA Sami HADDAD Professeur titulaire, Faculté de médecine, Université de Montréal Michel LAURENTIE Chef d’unité Expérimentation, Modélisation et Analyse de Données, Anses Raphaële LE GARREC Enseignant-chercheur, Université Bretagne Occidentale Dir. de thèse : Alain-Claude ROUDOT Professeur des Universités, Université Bretagne Occidentale Co-dir. de thèse : Jean Lou DORNE Senior Scientific Officer-Toxicologist, EFSA 1 The research described in this thesis was funded by a grant from the European Food Safety Authority (EFSA) [Contract number: GP/EFSA/SCER/2015/01] 3 Acknowledgments / Remerciements Je tiens à remercier le Professeur Alain-Claude Roudot de m’avoir orienté vers l’Anses et de m’avoir convaincu de l’intérêt de la modélisation en évaluation des risques. Je suis très reconnaissant à Monsieur Jean Lou Dorne pour avoir initié ce projet ainsi que pour tous les conseils qu’il a sus me donner au cours de ces trois années. Je remercie le Professeur Xavier Declèves de m’avoir fait l’honneur d’accepter la présidence de mon jury de thèse. Ainsi que Monsieur Michel Laurentie et le Professeur Sami Haddad d’avoir accepté d’examiner mes travaux de thèse et d’en être les rapporteurs. Je remercie Madame Raphaële Le Garrec de sa participation à mon jury de thèse de même que Monsieur Laurent Bodin. Merci encore à Laurent pour m’avoir initié aux modèles toxicocinétiques et tout particulièrement pour être venu me voir un jour en me disant «il y a un projet sympa qui va commencer, ça te dit de faire une thèse ? » ! Je tiens également à remercier tous les collaborateurs du projet TK-TD MoHV et en particulier Mme Emanuela Testai pour sa coordination. Merci à l'équipe de "The Crazy Monkey", Leonie Lautz et Emma Kasteel pour tout le travail que nous avons réalisé ensemble mais aussi pour leur soutien durant ce voyage vers la « next generation ». Merci à Monsieur Chris Roth pour son accueil au sein de l’unité méthodologie et études. Merci à Camille Béchaux pour ses conseils et son soutien. Merci pour tout ce que tu m’as enseigné, y compris comment escalader des blocs en salle ! Merci à ensemble de l’UME-UPO pour les moments de convivialité partagés et ces citations mémorables (« Je ne critique pas, je constate »). Merci à François Pouzaud pour m’avoir fait partager sa sagesse concernant les approches BMD et la méthode Lafay. Merci à ma famille pour leurs encouragements chaleureux. Et enfin merci à Aurélys pour m’avoir toujours encouragé et supporté ainsi qu’à notre petit cœur, Trystan, qui aura connu le stress de fin de thèse dès son arrivée dans notre vie. 4 Table of contents 1. GENERAL INTRODUCTION .................................................................................................................... 14 1.1. HUMAN RISK ASSESSMENT OF CHEMICALS ................................................................................................. 14 1.2. UNCERTAINTY FACTORS IN CHEMICAL RISK ASSESSMENT .............................................................................. 18 1.3. PHYSIOLOGICALLY BASED KINETIC MODELS ................................................................................................ 20 1.4. HIERARCHICAL BAYESIAN MODELS FOR THE META-ANALYSIS OF KINETIC DATA .................................................. 21 1.5. ENZYMES AND TRANSPORTERS INVOLVED IN ADME PROCESSES .................................................................... 22 1.6. NEEDS FOR RESEARCH AND IMPLEMENTATION OF KINETIC MODELS IN RISK ASSESSMENT..................................... 28 1.7. SCOPE AND AIM OF THIS THESIS .............................................................................................................. 29 2. AGGREGATE EXPOSURE OF THE ADULT FRENCH POPULATION TO PYRETHROIDS ................................ 31 ABSTRACT ..................................................................................................................................................... 32 2.1. INTRODUCTION ................................................................................................................................... 33 2.2. MATERIAL AND METHODS ..................................................................................................................... 34 2.2.1. Study population and biomonitoring data .................................................................................... 35 2.2.2. Permethrin exposure data ............................................................................................................. 36 2.2.3. Human aggregate PBPK model ..................................................................................................... 39 2.2.4. Software ........................................................................................................................................ 45 2.3. RESULTS ............................................................................................................................................ 46 2.3.1. Model calibration .......................................................................................................................... 46 2.3.2. Simulated cis- and trans-DCCA urinary excretion .......................................................................... 47 2.3.3. Contribution of sources and routes of exposure to simulated urinary concentrations of DCCA.... 49 2.4. DISCUSSION ........................................................................................................................................ 50 ACKNOWLEDGMENTS ...................................................................................................................................... 53 AUTHOR’S CONTRIBUTION ................................................................................................................................ 53 3. INTER-ETHNIC DIFFERENCES IN CYP3A4 METABOLISM: A BAYESIAN META-ANALYSIS FOR THE REFINEMENT OF UNCERTAINTY FACTORS IN CHEMICAL RISK ASSESSMENT ........................................ 55 ABSTRACT ..................................................................................................................................................... 56 3.1. INTRODUCTION ................................................................................................................................... 57 3.2. MATERIAL AND METHODS ..................................................................................................................... 58 3.2.1. Extensive Literature Search and Data collection ........................................................................... 58 3.2.2. Meta-analysis ................................................................................................................................ 60 3.2.3. Derivation of probabilistic CYP3A4-related uncertainty factors .................................................... 63 3.2.4. Software ........................................................................................................................................ 64 3.3. RESULTS ............................................................................................................................................ 64 3.3.1. Overview of data collection ........................................................................................................... 64 3.3.2. Inter-ethnic differences in CYP3A4 and CYP3A4-related uncertainty factors ................................ 66 3.3.3. Kinetic data for the elderly, children
Load more

Recommended publications
  • Report of the Advisory Group to Recommend Priorities for the IARC Monographs During 2020–2024
    IARC Monographs on the Identification of Carcinogenic Hazards to Humans Report of the Advisory Group to Recommend Priorities for the IARC Monographs during 2020–2024 Report of the Advisory Group to Recommend Priorities for the IARC Monographs during 2020–2024 CONTENTS Introduction ................................................................................................................................... 1 Acetaldehyde (CAS No. 75-07-0) ................................................................................................. 3 Acrolein (CAS No. 107-02-8) ....................................................................................................... 4 Acrylamide (CAS No. 79-06-1) .................................................................................................... 5 Acrylonitrile (CAS No. 107-13-1) ................................................................................................ 6 Aflatoxins (CAS No. 1402-68-2) .................................................................................................. 8 Air pollutants and underlying mechanisms for breast cancer ....................................................... 9 Airborne gram-negative bacterial endotoxins ............................................................................. 10 Alachlor (chloroacetanilide herbicide) (CAS No. 15972-60-8) .................................................. 10 Aluminium (CAS No. 7429-90-5) .............................................................................................. 11
    [Show full text]
  • National Center for Toxicological Research
    National Center for Toxicological Research Annual Report Research Accomplishments and Plans FY 2015 – FY 2016 Page 0 of 193 Table of Contents Preface – William Slikker, Jr., Ph.D. ................................................................................... 3 NCTR Vision ......................................................................................................................... 7 NCTR Mission ...................................................................................................................... 7 NCTR Strategic Plan ............................................................................................................ 7 NCTR Organizational Structure .......................................................................................... 8 NCTR Location and Facilities .............................................................................................. 9 NCTR Advances Research Through Outreach and Collaboration ................................... 10 NCTR Global Outreach and Training Activities ............................................................... 12 Global Summit on Regulatory Science .................................................................................................12 Training Activities .................................................................................................................................14 NCTR Scientists – Leaders in the Research Community .................................................. 15 Science Advisory Board ...................................................................................................
    [Show full text]
  • Chemistry and Safety of Acrylamide in Food ADVANCES in EXPERIMENTAL MEDICINE and BIOLOGY
    Chemistry and Safety of Acrylamide in Food ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY Editorial Board: NATHAN BACK, State University of New York at Buffalo IRUN R. COHEN, The Weizmann Institute of Science DAVID KRITCHEVSKY, Wistar Institute ABEL LAJTHA, N. S. Kline Institute for Psychiatric Research RODOLFO PAOLETTI, University of Milan Recent Volumes in this Series Volume 553 BIOMATERIALS: From Molecules to Engineered Tissues Edited by Nesrin Hasirci and Vasif Hasirci Volume 554 PROTECTING INFANTS THROUGH HUMAN MILK: Advancing the Scientific Evidence Edited by Larry K. Pickering, Ardythe L. Morrow, Guillermo M. Ruiz-Palacios, and Richard J. Schanler Volume 555 BREAST FEEEDING: Early Influences on Later Health Edited by Gail Goldberg, Andrew Prentice, Ann Prentice, Suzanne Filteau, and Elsie Widdowson Volume 556 IMMUNOINFORMATICS: Opportunities and Challenges of Bridging Immunology with Computer and Information Sciences Edited by Christian Schoenbach, V. Brusic, and Akihiko Konagaya Volume 557 BRAIN REPAIR Edited by M. Bahr Volume 558 DEFECTS OF SECRETION IN CYSTIC FIBROSIS Edited by Carsten Schultz Volume 559 CELL VOLUME AND SIGNALING Edited by Peter K. Lauf and Norma C. Adragna Volume 560 MECHANISMS OF LYMPHOCYTE ACTIVATION AND IMMUNE REGULATION X: INNATE IMMUNITY Edited by Sudhir Gupta, William Paul, and Ralph Steinman Volume 561 CHEMISTRY AND SAFETY OF ACRYLAMIDE IN FOOD Edited by Mendel Friedman and Don Mottram A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact the publisher. Chemistry and Safety of Acrylamide in Food Edited by Mendel Friedman Agricultural Research Service, USDA Albany, California and Don Mottram University of Reading Reading, United Kingdom Spriinge r Library of Congress Cataloging-in-Publication Data Chemistry and safety of acrylamide in food/edited by Mendel Friedman and Don Mottram.
    [Show full text]
  • Dietary Intake and Biomarkers of Acrylamide Exposure and Risk of Endometrial and Ovarian Cancer
    Dietary intake and biomarkers of acrylamide exposure and risk of endometrial and ovarian cancer A molecular epidemiologic study in the European Prospective Investigation into Cancer and Nutrition Mireia Obón Santacana Aquesta tesi doctoral està subjecta a la llicència Reconeixement- NoComercial – SenseObraDerivada 3.0. Espanya de Creative Commons. Esta tesis doctoral está sujeta a la licencia Reconocimiento - NoComercial – SinObraDerivada 3.0. España de Creative Commons. This doctoral thesis is licensed under the Creative Commons Attribution-NonCommercial- NoDerivs 3.0. Spain License. REFERENCE LIST REFERENCE LIST 8. REFERENCE LIST 1. (1986) Acrylamide. IARC Monogr Eval Carcinog Risk Chem Hum 39:41–66. 2. Chen Y-H, Xia E-Q, Xu X-R, et al (2012) Evaluation of Acrylamide in Food from China by a LC/MS/MS Method. Int J Environ Res Public Health 9:4150–4158. doi: 10.3390/ijerph9114150 3. IARC (1994) IARC working group on the evaluation of carcinogenic risks to humans: some industrial chemicals. Lyon, 15-22 February 1994. IARC Monogr EvalCarcinogRisks Hum 60:1–560. 4. Sobel W, Bond GG, Parsons TW, Brenner FE (1986) Acrylamide cohort mortality study. Br J Ind Med 43:785–788. 5. Collins JJ, Swaen GM, Marsh GM, et al (1989) Mortality patterns among workers exposed to acrylamide. J Occup Med 31:614–617. 6. Le Quesne PM (1985) Clinical and morphological findings in acrylamide toxicity. Neurotoxicology 6:17–24. 7. Reynolds T (2002) Acrylamide and cancer: tunnel leak in Sweden prompted studies. J Natl Cancer Inst 94:876–878. 8. Törnqvist M, Bergmark E, Ehrenberg L, Granath F (1998) Risk assessment of acrylamide.
    [Show full text]
  • National Center for Toxicological Research Annual Report 2019
    National Center for Toxicological Research 2019 Annual Report Vision, Mission, and Goals Vision The U.S. Food and Drug Administration’s National Center for Toxicological Research is a global resource for collaboration—providing consultation, training, and innovative scientific solutions in support of FDA’s mission to improve public health. Mission NCTR conducts scientific research to generate data for FDA decision making, and develops and supports innovative tools and approaches that FDA uses to protect and promote individual and public health. NCTR Research Goals 2019 NCTR Annual Report Table of Contents (Please click on any of the sections below to quickly visit that section) 4 Preface ─ Message from the Director 5 Preface ─ About the Annual Report 6 NCTR Organization Structure ─ NCTR Leadership 7 NCTR Organization Structure ─ Research Division Directors 8 NCTR at a Glance 9 NCTR at a Glance ─ Numbers for 2019 12 2019 Research Collaborations 13 Collaborations ─ CDER 15 Collaborations ─ CTP 16 Collaborations ─ CFSAN 17 Collaborations ─ CVM 18 Collaborations ─ ORA 19 Collaborations ─ NIEHS/NTP 20 Science Advisory Board 21 Perinatal Health Center of Excellence 22 Global Summit on Regulatory Science (GSRS) 23 2019 NCTR Research Divisions and Important Accomplishments 24 Biochemical Toxicology 26 Bioinformatics & Biostatistics 28 Genetic & Molecular Toxicology 30 Microbiology 32 Neurotoxicology 34 Systems Biology 36 Office of Scientific Coordination www.fda.gov/nctr Message from the Director Preface The National Center for Toxicological Research (NCTR) is the U.S. Food and Drug Administration’s (FDA) premier laboratory research center focused on all FDA-regulated products. NCTR’s primary goal is to support FDA, a critical component of the Department of Health and Human Services (HHS), in its efforts to promote and protect the health of the American public.
    [Show full text]
  • Acrylamide in Food
    COUNCIL FORFOR AGRICULTURALAGRICULTURAL SCIENCE SCIENCE AND AND TECHNOLOGY—1 TECHNOLOGY NUMBER 32 JUNE 2006 ACRYLAMIDE IN FOOD TASK FORCE MEMBERS: David Lineback, Co- chair, Joint Institute for Food Safety and Applied INTRODUCTION Nutrition, University of Maryland, College Park; studies or from human expo- In April 2002, researchers Michael W. Pariza, Cochair, Food Research sure in the workplace. Before at the Swedish National Food the Swedish study, no data Institute, University of Wisconsin, Madison; Administration and Stockholm were available on the effects of University, using a new analyti- James Coughlin, Coughlin & Associates, La- acrylamide at the low concen- cal procedure, announced they guna Niguel, California; Catherine Davies, trations observed in food (i.e., had discovered the presence of Department of Animal and Food Sciences, Uni- in the microgram (µg)/kilo- acrylamide in foods prepared versity of Delaware, Newark; Beate Kettlitz,* gram (kg) [parts per billion by heating (frying, baking) at BEUC, the European Consumers’ Organization, (ppb)] range). temperatures above 120°C So acrylamide is not new, Brussels, Belgium; Lauren Posnick Robin, (Swedish 2002; Tareke et al. but its presence in food is 2002). Identification of Center for Food Safety and Applied Nutrition, newly discovered. Increased acrylamide in these foods, U.S. Food and Drug Administration, College concern about the effect of which include french fries, po- Park, Maryland; David Schmidt, International acrylamide on human health tato chips (crisps), cookies (bis-
    [Show full text]
  • Using 21St Century Science to Improve Risk-Related Evaluations (2017)
    THE NATIONAL ACADEMIES PRESS This PDF is available at http://nap.edu/24635 SHARE Using 21st Century Science to Improve Risk-Related Evaluations (2017) DETAILS 200 pages | 8.5 x 11 | PAPERBACK ISBN 978-0-309-45348-6 | DOI 10.17226/24635 CONTRIBUTORS GET THIS BOOK Committee on Incorporating 21st Century Science into Risk-Based Evaluations; Board on Environmental Studies and Toxicology; Division on Earth and Life Studies; National Academies of Sciences, Engineering, and Medicine FIND RELATED TITLES SUGGESTED CITATION National Academies of Sciences, Engineering, and Medicine 2017. Using 21st Century Science to Improve Risk-Related Evaluations. Washington, DC: The National Academies Press. https://doi.org/10.17226/24635. Visit the National Academies Press at NAP.edu and login or register to get: – Access to free PDF downloads of thousands of scientific reports – 10% off the price of print titles – Email or social media notifications of new titles related to your interests – Special offers and discounts Distribution, posting, or copying of this PDF is strictly prohibited without written permission of the National Academies Press. (Request Permission) Unless otherwise indicated, all materials in this PDF are copyrighted by the National Academy of Sciences. Copyright © National Academy of Sciences. All rights reserved. Using 21st Century Science to Improve Risk-Related Evaluations USING 21ST CENTURY SCIENCE TO IMPROVE RISK-RELATED EVALUATIONS Committee on Incorporating 21st Century Science into Risk-Based Evaluations Board on Environmental Studies and Toxicology Division on Earth and Life Studies A Report of Copyright National Academy of Sciences. All rights reserved. Using 21st Century Science to Improve Risk-Related Evaluations THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001 This activity was supported by Contract EP-C-14-005, TO#0002 between the National Academy of Sciences and the US Environmental Protection Agency.
    [Show full text]
  • Genotoxicity of Acrylamide and Glycidamide: a Review of the Studies by HPRT Gene and TK Gene Mutation Assays
    Genes and Environment, Vol. 34, No. 1 pp. 1–8 (2012) Review Genotoxicity of Acrylamide and Glycidamide: A Review of the Studies by HPRT Gene and TK Gene Mutation Assays Lin Ao1,2 and Jia Cao1,2,3 1Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China 2Key Laboratory of Electromagnetic Radiation Damage and Medical Protection, Ministry of Education of China, Chongqing, PR China (Received September 19, 2011; Revised December 6, 2011; Accepted December 28, 2011) Acrylamide (AA), a proven rodent carcinogen, is found very high temperatures, as a result of Maillard reactions in a variety of commonly consumed human foods, which involving asparagine and reducing sugars (3). Total die- has raised public health concerns. AA is largely oxidized to tary daily AA intake has been estimated to correspond the chemically reactive epoxide, glycidamide (GA), by to about 0.5 mg AA per kg body weight on the basis of a cytochrome P450 2E1. The genotoxic eŠects of AA and normal western diet (4,5). In 2002, a consultation held GA have been extensively evaluated. However, the results by the Food and Agriculture Organization of the United in mammalian gene mutation tests were inconsistent, es- Nations(FAO)andtheWorldHealthOrganization pecially the genotoxic eŠects at the HPRT gene and TK gene. In this article, the relevant mutations induced by AA (WHO) concluded that AA represented a ``major prob- and GA on both gene loci in various test systems involving lem'', because of the relative high levels in these foods in vivo and in vitro tests are reviewed.
    [Show full text]
  • Obesity and Endocrine-Disrupting Chemicals
    ID: 20-0578 10 2 A A Amato et al. Obesity and endocrine 10:2 R87–R105 disrupting chemicals REVIEW Obesity and endocrine-disrupting chemicals Angelica Amorim Amato1,2, Hailey Brit Wheeler2 and Bruce Blumberg2,3,4 1Department of Pharmaceutical Sciences, University of Brasilia, Brasilia, Brazil 2Department of Developmental and Cell Biology, University of California, Irvine, California, USA 3Department of Pharmaceutical Sciences, University of California, Irvine, California, USA 4Department of Biomedical Engineering, University of California, Irvine, California, USA Correspondence should be addressed to B Blumberg: [email protected] Abstract Obesity is now a worldwide pandemic. The usual explanation given for the prevalence of Key Words obesity is that it results from consumption of a calorie dense diet coupled with physical f obesogen inactivity. However, this model inadequately explains rising obesity in adults and in f endocrine-disrupting children over the past few decades, indicating that other factors must be important chemical contributors. An endocrine-disrupting chemical (EDC) is an exogenous chemical, or mixture f EDC that interferes with any aspect of hormone action. EDCs have become pervasive in our f transgenerational environment, allowing humans to be exposed daily through ingestion, inhalation, and f adipogenesis direct dermal contact. Exposure to EDCs has been causally linked with obesity in model f obesity organisms and associated with obesity occurrence in humans. Obesogens promote adipogenesis and obesity, in vivo, by a variety of mechanisms. The environmental obesogen model holds that exposure to obesogens elicits a predisposition to obesity and that such exposures may be an important yet overlooked factor in the obesity pandemic. Effects produced by EDCs and obesogen exposure may be passed to subsequent, unexposed generations.
    [Show full text]
  • Dietary Intake of Acrylamide and Risk of Breast, Endometrial and Ovarian Cancers: a Systematic Review and Dose-Response Meta-Analysis
    Author Manuscript Published OnlineFirst on March 13, 2020; DOI: 10.1158/1055-9965.EPI-19-1628 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Title: Dietary intake of acrylamide and risk of breast, endometrial and ovarian cancers: A systematic review and dose-response meta-analysis Authors: Giorgia Adani1, Tommaso Filippini1, Lauren A Wise2, Thorhallur I Halldorsson3,4, Ludek Blaha5, Marco Vinceti1,2* Affiliations: 1Environmental, Genetic and Nutritional Epidemiology Research Center (CREAGEN), Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; 2Department of Epidemiology, Boston University School of Public Health, Boston, USA; 3Centre for Fetal Programming, Department of Epidemiology Research, Copenhagen, Denmark; 4Unit for Nutrition Research, Faculty of Food Science and Nutrition, University of Iceland, Reykjavík, Iceland. 5Masaryk University, Faculty of Science, RECETOX, Brno, Czech Republic. Running title: Acrylamide and breast, endometrial and ovarian cancer risk Keywords: acrylamide; dietary intake; breast cancer; endometrial cancer; ovarian cancer; dose- response meta-analysis *Corresponding author: Marco Vinceti, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Via Campi 287, 41125 Modena, Italy. E-mail address: [email protected] Declarations of interest: The authors declare no potential conflicts of interest. Financial support: This work was supported by the European Union Horizon-2020 Research and Innovation Programme under grant agreement No. 733032 HBM4EU. 1 Downloaded from cebp.aacrjournals.org on October 1, 2021. © 2020 American Association for Cancer Research. Author Manuscript Published OnlineFirst on March 13, 2020; DOI: 10.1158/1055-9965.EPI-19-1628 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
    [Show full text]
  • Experimental Analysis of Exome-Scale Mutational Signature of Glycidamide, the Reactive Metabolite of Acrylamide
    bioRxiv preprint doi: https://doi.org/10.1101/254664; this version posted January 27, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. Title Experimental analysis of exome-scale mutational signature of glycidamide, the reactive metabolite of acrylamide Authors Maria Zhivagui1, Maude Ardin1, Alvin W. T. Ng2,3,4, Mona I. Churchwell5, Manuraj Pandey1, Stephanie Villar1, Vincent Cahais6, Alexis Robitaille7, Liacine Bouaoun8, Adriana Heguy9, Kathryn Guyton10, Martha R. Stampfer11, James McKay12, Monica Hollstein1,13,14, Magali Olivier1, Steven G. Rozen2,3, Frederick A. Beland5, Michael Korenjak1 and Jiri Zavadil1 Affiliations 1 Molecular Mechanisms and Biomarkers Group, International Agency for Research on Cancer, Lyon 69008, France 2 Centre for Computational Biology, Duke-NUS Medical School, Singapore 169857, Singapore 3 Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, 169857, Singapore 4 NUS Graduate School for Integrative Sciences and Engineering, 117456, Singapore 5 Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA 6 Epigenetics Group, International Agency for Research on Cancer, Lyon 69008, France 7 Infections and Cancer Biology Group, International Agency for Research on Cancer, Lyon 69008, France 8 Environment and Radiation Section, International Agency for Research on Cancer,
    [Show full text]
  • Preconceptional Paternal Glycidamide Exposure Affects Embryonic Gene
    Reproductive Toxicology 32 (2011) 463–471 Contents lists available at SciVerse ScienceDirect Reproductive Toxicology jo urnal homepage: www.elsevier.com/locate/reprotox Preconceptional paternal glycidamide exposure affects embryonic gene expression: Single embryo gene expression study following in vitro fertilization a,∗ b a a a Asgeir Brevik , Vendula Rusnakova , Nur Duale , Hege Holte Slagsvold , Ann-Karin Olsen , c d a a Ritsa Storeng , Mikael Kubista , Gunnar Brunborg , Birgitte Lindeman a Norwegian Institute of Public Health, Division of Environmental Medicine, Department of Chemical Toxicology, P.O. Box 4404, Nydalen, N-0403 Oslo, Norway b Dept. of Gene Expression, Institute of Biotechnology AS CR, v.v.i., Videnska 1083, Prague 4, 142 20, Czech Republic c Oslo University Hospital - Rikshospitalet, 0027 Oslo, Norway d Tataa Biocenter, Odinsgatan 28, 411 03 Göteborg, Sweden a r t i c l e i n f o a b s t r a c t Article history: Recognition of early determinants of disease onset has sparked an interest in paternally transmitted Received 2 March 2011 factors and their impact on the developing embryo. Acrylamide (AA), a widely distributed xenobiotic Received in revised form 10 August 2011 compound, is converted to its active metabolite glycidamide (GA) by the CYP2E1 enzyme. Based on its Accepted 17 September 2011 capacity to induce dominant lethal mutations, we hypothesized that paternal GA exposure would have Available online 29 September 2011 a negative impact on embryonic genome activation, via GA-DNA and protamine adducts persisting in the fertilizing sperm. Using a combination of in vitro fertilization (IVF) techniques and RT-qPCR single Keywords: embryo gene expression (SEGE), we studied the expression of key DNA repair genes and genes important Single-cell gene expression Glycidamide for embryo development, at the 1-, 2-, 4- and 8-cell stage of the developing mouse embryo.
    [Show full text]