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    Carcinogenesis. 2015 Jun 24. pii: bgv039. doi: 10.1093/carcin/bgv039. pmc: PMC4480130
    Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.
    Goodson WH1,  Lowe L2,  Carpenter DO3,  Gilbertson M4,  Manaf Ali A5,  Lopez de Cerain Salsamendi A6,  Lasfar A7,  Carnero A8,  Azqueta A9,  Amedei A10,  Charles AK11,  Collins AR12,  Ward A13,  Salzberg AC14,  Colacci A15,  Olsen AK16,  Berg A17,  Barclay BJ18,  Zhou BP19,  Blanco-Aparicio C20,  Baglole CJ21,  Dong C22,  Mondello C23,  Hsu CW24,  Naus CC25,  Yedjou C26,  Curran CS27,  Laird DW28,  Koch DC29,  Carlin DJ30,  Felsher DW31,  Roy D32,  Brown DG33,  Ratovitski E34,  Ryan EP35,  Corsini E36,  Rojas E37,  Moon EY38,  Laconi E39,  Marongiu F40,  Al-Mulla F41,  Chiaradonna F42,  Darroudi F43,  Martin FL44,  Van Schooten FJ45,  Goldberg GS46,  Wagemaker G47,  Nangami GN48,  Calaf GM49,  Williams G50,  Wolf GT51,  Koppen G52,  Brunborg G53,  Lyerly HK54,  Krishnan H55,  Ab Hamid H56,  Yasaei H57,  Sone H58,  Kondoh H59,  Salem HK60,  Hsu HY61,  Park HH62,  Koturbash I63,  Miousse IR64,  Scovassi AI65,  Klaunig JE66,  Vondráček J67,  Raju J68,  Roman J69,  Wise JP70,  Whitfield JR71,  Woodrick J72,  Christopher JA73,  Ochieng J74,  Martinez-Leal JF75,  Weisz J76,  Kravchenko J77,  Sun J78,  Prudhomme KR79,  Narayanan KB80,  Cohen-Solal KA81,  Moorwood K82,  Gonzalez L83,  Soucek L84,  Jian L85,  D'Abronzo LS86,  Lin LT87,  Li L88,  Gulliver L89,  McCawley LJ90,  Memeo L91,  Vermeulen L92,  Leyns L93,  Zhang L94,  Valverde M95,  Khatami M96,  Romano MF97,  Chapellier M98,  Williams MA99,  Wade M100,  Manjili MH101,  Lleonart ME102,  Xia M103,  Gonzalez MJ104,  Karamouzis MV105,  Kirsch-Volders M106,  Vaccari M107,  Kuemmerle NB108,  Singh N109,  Cruickshanks N110,  Kleinstreuer N111,  van Larebeke N112,  Ahmed N113,  Ogunkua O114,  Krishnakumar PK115,  Vadgama P116,  Marignani PA117,  Ghosh PM118,  Ostrosky-Wegman P119,  Thompson PA120,  Dent P121,  Heneberg P122,  Darbre P123,  Sing Leung P124,  Nangia-Makker P125,  Cheng QS126,  Robey RB127,  Al-Temaimi R128,  Roy R129,  Andrade-Vieira R130,  Sinha RK131,  Mehta R132,  Vento R133,  Di Fiore R134,  Ponce-Cusi R135,  Dornetshuber-Fleiss R136,  Nahta R137,  Castellino RC138,  Palorini R139,  Abd Hamid R140,  Langie SA141,  Eltom SE142,  Brooks SA143,  Ryeom S144,  Wise SS145,  Bay SN146,  Harris SA147,  Papagerakis S148,  Romano S149,  Pavanello S150,  Eriksson S151,  Forte S152,  Casey SC153,  Luanpitpong S154,  Lee TJ155,  Otsuki T156,  Chen T157,  Massfelder T158,  Sanderson T159,  Guarnieri T160,  Hultman T161,  Dormoy V162,  Odero-Marah V163,  Sabbisetti V164,  Maguer-Satta V165,  Rathmell WK166,  Engström W167,  Decker WK168,  Bisson WH169,  Rojanasakul Y170,  Luqmani Y171,  Chen Z172,  Hu Z173
    Author information
    1California Pacific Medical Center Research Institute, 2100 Webster Street #401, San Francisco, CA 94115, USA, Getting to Know Cancer, Room 229A, 36 Arthur Street, Truro, Nova Scotia B2N 1X5, Canada, Lancaster Environment Centre, Lancaster University, Bailrigg, Lancaster LA1 4AP, UK, Institute for Health and the Environment, University at Albany, 5 University Pl., Rensselaer, NY 12144, USA, Getting to Know Cancer, Guelph N1G 1E4, Canada, School of Biotechnology, Faculty of Agriculture Biotechnology and Food Sciences, Sultan Zainal Abidin University, Tembila Campus, 22200 Besut, Terengganu, Malaysia, Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Navarra, Pamplona 31008, Spain, Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers, State University of New Jersey, Piscataway, NJ 08854, USA, Instituto de Biomedicina de Sevilla, Consejo Superior de Investigaciones Cientificas. Hospital Universitario Virgen del Rocio, Univ. de Sevilla., Avda Manuel Siurot sn. 41013 Sevilla, Spain, Department of Experimental and Clinical Medicine, University of Firenze, Florence 50134, Italy, School of Biological Sciences, University of Reading, Hopkins Building, Reading, Berkshire RG6 6UB, UK, Department of Nutrition, University of Oslo, Oslo, Norway, Department of Biochemistry and Biology, University of Bath, Claverton Down, Bath BA2 7AY, UK, Department of Public Health Sciences, College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA, Center for Environmental Carcinogenesis and Risk Assessment, Environmental Protection and Health Prevention Agency, 40126 Bologna, Italy, Department of Chemicals and Radiation, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo N-0403, Norway, Planet Biotechnologies Inc., St Albert, Alberta T8N 5K4, Canada, Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40508, USA, Spanish National Cancer Research Centre, CNI
    2Getting to Know Cancer, Room 229A, 36 Arthur Street, Truro, Nova Scotia B2N 1X5, Canada, Lancaster Environment Centre, Lancaster University, Bailrigg, Lancaster LA1 4AP, UK.
    3Institute for Health and the Environment, University at Albany, 5 University Pl., Rensselaer, NY 12144, USA.
    4Getting to Know Cancer, Guelph N1G 1E4, Canada.
    5School of Biotechnology, Faculty of Agriculture Biotechnology and Food Sciences, Sultan Zainal Abidin University, Tembila Campus, 22200 Besut, Terengganu, Malaysia.
    6Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Navarra, Pamplona 31008, Spain.
    7Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers, State University of New Jersey, Piscataway, NJ 08854, USA.
    8Instituto de Biomedicina de Sevilla, Consejo Superior de Investigaciones Cientificas. Hospital Universitario Virgen del Rocio, Univ. de Sevilla., Avda Manuel Siurot sn. 41013 Sevilla, Spain.
    9Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Navarra, Pamplona 31008, Spain.
    10Department of Experimental and Clinical Medicine, University of Firenze, Florence 50134, Italy.
    11School of Biological Sciences, University of Reading, Hopkins Building, Reading, Berkshire RG6 6UB, UK.
    12Department of Nutrition, University of Oslo, Oslo, Norway.
    13Department of Biochemistry and Biology, University of Bath, Claverton Down, Bath BA2 7AY, UK.
    14Department of Public Health Sciences, College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA.
    15Center for Environmental Carcinogenesis and Risk Assessment, Environmental Protection and Health Prevention Agency, 40126 Bologna, Italy.
    16Department of Chemicals and Radiation, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo N-0403, Norway.
    17Department of Public Health Sciences, College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA.
    18Planet Biotechnologies Inc., St Albert, Alberta T8N 5K4, Canada.
    19Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40508, USA.
    20Spanish National Cancer Research Centre, CNIO, Melchor Fernandez Almagro, 3, 28029 Madrid, Spain.
    21Department of Medicine, McGill University, Montreal, Quebec H4A 3J1, Canada.
    22Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40508, USA.
    23Istituto di Genetica Molecolare, CNR, Via Abbiategrasso 207, 27100 Pavia, Italy.
    24Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Bethesda, MD 20892-3375, USA.
    25Department of Cellular and Physiological Sciences, Life Sciences Institute, Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia V5Z 1M9, Canada.
    26Department of Biology, Jackson State University, Jackson, MS 39217, USA.
    27Department of Molecular and Environmental Toxicology, University of Wisconsin-Madison, Madison, WI 53706, USA.
    28Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario N6A 3K7, Canada.
    29Stanford University Department of Medicine, Division of Oncology, Stanford, CA 94305, USA.
    30Superfund Research Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27560, USA.
    31Department of Medicine, Oncology and Pathology, Stanford University, Stanford, CA 94305, USA.
    32Department of Natural Science, The City University of New York at Hostos Campus, Bronx, NY 10451, USA.
    33Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523-1680, USA.
    34Department of Head and Neck Surgery/Head and Neck Cancer Research, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
    35Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523-1680, USA.
    36Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy.
    37Department of Genomic Medicine and Environmental Toxicology, Institute for Biomedical Research, National Autonomous University of Mexico, Mexico City 04510, México.
    38Department of Bioscience and Biotechnology, Sejong University, Seoul 143-747, Korea.
    39Department of Biomedical Sciences, University of Cagliari, 09124 Cagliari, Italy.
    40Department of Biomedical Sciences, University of Cagliari, 09124 Cagliari, Italy.
    41Department of Pathology, Kuwait University, Safat 13110, Kuwait.
    42Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy, SYSBIO Centre of Systems Biology, Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy.
    43Human Safety and Environmental Research, Department of Health Sciences, College of North Atlantic, Doha 24449, State of Qatar.
    44Lancaster Environment Centre, Lancaster University, Bailrigg, Lancaster LA1 4AP, UK.
    45Department of Toxicology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht 6200, The Netherlands.
    46Department of Molecular Biology, School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USA.
    47Hacettepe University, Center for Stem Cell Research and Development, Ankara 06640, Turkey.
    48Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208, USA.
    49Center for Radiological Research, Columbia University Medical Center, New York, NY 10032, USA, Instituto de Alta Investigacion, Universidad de Tarapaca, Arica, Chile.
    50School of Biological Sciences, University of Reading, Reading, RG6 6UB, UK.
    51Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
    52Environmental Risk and Health Unit, Flemish Institute for Technological Research, 2400 Mol, Belgium.
    53Department of Chemicals and Radiation, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo N-0403, Norway.
    54Department of Surgery, Pathology, Immunology, Duke University Medical Center, Durham, NC 27710, USA.
    55Department of Molecular Biology, School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USA.
    56Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, 43400 Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
    57Department of Life Sciences, College of Health and Life Sciences and the Health and Environment Theme, Institute of Environment, Health and Societies, Brunel University Kingston Lane, Uxbridge, Middlesex UB8 3PH, UK.
    58National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibraki 3058506, Japan.
    59Department of Geriatric Medicine, Kyoto University Hospital 54 Kawaharacho, Shogoin, Sakyo-ku Kyoto, 606-8507, Japan.
    60Department of Urology, Kasr Al-Ainy School of Medicine, Cairo University, El Manial, Cairo 11559, Egypt.
    61Department of Life Sciences, Tzu-Chi University, Hualien 970, Taiwan.
    62School of Biotechnology, Yeungnam University, Gyeongbuk 712-749, South Korea.
    63Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
    64Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
    65Istituto di Genetica Molecolare, CNR, Via Abbiategrasso 207, 27100 Pavia, Italy.
    66Department of Environmental Health, Indiana University, School of Public Health, Bloomington, IN 47405, USA.
    67Department of Cytokinetics, Institute of Biophysics Academy of Sciences of the Czech Republic, Brno, CZ-61265, Czech Republic.
    68Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Canada, Ottawa, Ontario K1A 0K9, Canada.
    69Department of Medicine, University of Louisville, Louisville, KY 40202, USA, Robley Rex VA Medical Center, Louisville, KY 40202, USA.
    70Department of Applied Medical Sciences, University of Southern Maine, 96 Falmouth St., Portland, ME 04104, USA.
    71Mouse Models of Cancer Therapies Group, Vall d'Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain.
    72Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC 20057, USA.
    73Cancer Research UK. Cambridge Institute, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK.
    74Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208, USA.
    75Department of Cell Biology, Pharmamar-SAU, Avda. De los Reyes, 1. 28770-Colmenar Viejo, Madrid, Spain.
    76Departments of Obstetrics and Gynecology and Pathology, Pennsylvania State University College of Medicine, Hershey PA 17033, USA.
    77Department of Surgery, Pathology, Immunology, Duke University Medical Center, Durham, NC 27710, USA.
    78Department of Biochemistry, Rush University, Chicago, IL 60612, USA.
    79Environmental and Molecular Toxicology, Environmental Health Science Center, Oregon State University, Corvallis, OR 97331, USA.
    80School of Biotechnology, Yeungnam University, Gyeongbuk 712-749, South Korea.
    81Department of Medicine/Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
    82Department of Biochemistry and Biology, University of Bath, Claverton Down, Bath BA2 7AY, UK.
    83Laboratory for Cell Genetics, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
    84Mouse Models of Cancer Therapies Group, Vall d'Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain, Catalan Institution for Research and Advanced Studies (ICREA), Barcelona 08010, Spain.
    85School of Public Health, Curtin University, Bentley, WA 6102, Australia, Department of Urology, University of California Davis, Sacramento, CA 95817, USA.
    86Department of Urology, University of California Davis, Sacramento, CA 95817, USA.
    87Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
    88School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, The People's Republic of China.
    89Faculty of Medicine, University of Otago, Dunedin 9054, New Zealand.
    90Department of Biomedical Engineering and Cancer Biology, Vanderbilt University, Nashville, TN 37235, USA.
    91Department of Experimental Oncology, Mediterranean Institute of Oncology, Via Penninazzo 7, Viagrande (CT) 95029, Italy.
    92Center for Experimental Molecular Medicine, Academic Medical Center, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands.
    93Laboratory for Cell Genetics, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
    94Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA 94720-7360, USA.
    95Department of Genomic Medicine and Environmental Toxicology, Institute for Biomedical Research, National Autonomous University of Mexico, Mexico City 04510, México.
    96Inflammation and Cancer Research, National Cancer Institute (NCI) (Retired), National Institutes of Health, Bethesda, MD 20892, USA.
    97Department of Molecular Medicine and Medical Biotechnology, Federico II University of Naples, 80131 Naples, Italy.
    98Centre De Recherche En Cancerologie, De Lyon, Lyon, U1052-UMR5286, France.
    99United States Army Institute of Public Health, Toxicology Portfolio-Health Effects Research Program, Aberdeen Proving Ground, Edgewood, MD 21010-5403, USA.
    100Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia, Via Adamello 16, 20139 Milano, Italy.
    101Department of Microbiology and Immunology, Virginia Commonwealth University, Massey Cancer Center, Richmond, VA 23298, USA.
    102Institut De Recerca Hospital Vall D'Hebron, Passeig Vall d'Hebron, 119-129, 08035 Barcelona, Spain.
    103Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Bethesda, MD 20892-3375, USA.
    104University of Puerto Rico, Medical Sciences Campus, School of Public Health, Nutrition Program, San Juan 00921, Puerto Rico.
    105Department of Biological Chemistry, Medical School, University of Athens, Institute of Molecular Medicine and Biomedical Research, 10676 Athens, Greece.
    106Laboratory for Cell Genetics, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
    107Center for Environmental Carcinogenesis and Risk Assessment, Environmental Protection and Health Prevention Agency, 40126 Bologna, Italy.
    108Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
    109Advanced Molecular Science Research Centre (Centre for Advanced Research), King George's Medical University, Lucknow, Uttar Pradesh 226 003, India.
    110Departments of Neurosurgery and Biochemistry and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.
    111Integrated Laboratory Systems Inc., in support of the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, RTP, NC 27709, USA.
    112Analytische, Milieu en Geochemie, Vrije Universiteit Brussel, Brussel B1050, Belgium.
    113Department of Obstetrics and Gynecology, University of Melbourne, Victoria 3052, Australia.
    114Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208, USA.
    115Center for Environment and Water, Research Institute, King Fahd University of Petroleum and Minerals, Dhahran 3126, Saudi Arabia .
    116School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London, E1 4NS, UK.
    117Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada.
    118Department of Urology, University of California Davis, Sacramento, CA 95817, USA.
    119Department of Genomic Medicine and Environmental Toxicology, Institute for Biomedical Research, National Autonomous University of Mexico, Mexico City 04510, México.
    120Department of Pathology, Stony Brook School of Medicine, Stony Brook University, The State University of New York, Stony Brook, NY 11794-8691, USA.
    121Departments of Neurosurgery and Biochemistry and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.
    122Charles University in Prague, Third Faculty of Medicine, CZ-100 00 Prague 10, Czech Republic.
    123School of Biological Sciences, The University of Reading, Whiteknights, Reading RG6 6UB, England.
    124School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, The People's Republic of China.
    125Department of Pathology, Wayne State University, Detroit, MI 48201, USA.
    126Computer Science Department, Southern Illinois University, Carbondale, IL 62901, USA.
    127White River Junction Veterans Affairs Medical Center, White River Junction, VT 05009, USA, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
    128Human Genetics Unit, Department of Pathology, Faculty of Medicine, Kuwait University, Jabriya 13110, Kuwait.
    129Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC 20057, USA.
    130Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada.
    131Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
    132Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Canada, Ottawa, Ontario K1A 0K9, Canada.
    133Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies, Polyclinic Plexus, University of Palermo, Palermo 90127, Italy , Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA 19122, USA.
    134Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies, Polyclinic Plexus, University of Palermo, Palermo 90127, Italy .
    135Instituto de Alta Investigacion, Universidad de Tarapaca, Arica, Chile.
    136Department of Pharmacology and Toxicology, University of Vienna, Vienna A-1090, Austria, Institute of Cancer Research, Department of Medicine, Medical University of Vienna, Wien 1090, Austria.
    137Departments of Pharmacology and Hematology and Medical Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA 30322, USA.
    138Division of Hematology and Oncology, Department of Pediatrics, Children's Healthcare of Atlanta, GA 30322, USA, Department of Pediatrics, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA.
    139Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy, SYSBIO Centre of Systems Biology, Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy.
    140Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, 43400 Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
    141Environmental Risk and Health Unit, Flemish Institute for Technological Research, 2400 Mol, Belgium.
    142Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208, USA.
    143Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC 27599, USA.
    144Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
    145Department of Applied Medical Sciences, University of Southern Maine, 96 Falmouth St., Portland, ME 04104, USA.
    146Program in Genetics and Molecular Biology, Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, GA 30322, USA.
    147Population Health and Prevention, Research, Prevention and Cancer Control, Cancer Care Ontario, Toronto, Ontario, M5G 2L7, Canada, Departments of Epidemiology and Occupational and Environmental Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, M5T 3M7, Canada .
    148Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
    149Department of Molecular Medicine and Medical Biotechnology, Federico II University of Naples, 80131 Naples, Italy.
    150Department of Cardiac, Thoracic and Vascular Sciences, Unit of Occupational Medicine, University of Padova, Padova 35128, Italy.
    151Department of Anatomy, Physiology and Biochemistry, The Swedish University of Agricultural Sciences, PO Box 7011, VHC, Almas Allé 4, SE-756 51, Uppsala, Sweden.
    152Department of Experimental Oncology, Mediterranean Institute of Oncology, Via Penninazzo 7, Viagrande (CT) 95029, Italy.
    153Stanford University Department of Medicine, Division of Oncology, Stanford, CA 94305, USA.
    154Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
    155Department of Anatomy, College of Medicine, Yeungnam University, Daegu 705-717, South Korea.
    156Department of Hygiene, Kawasaki Medical School, Matsushima Kurashiki, Okayama 701-0192, Japan.
    157Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, United States Food and Drug Administration, Jefferson, AR 72079, USA.
    158INSERM U1113, team 3 'Cell Signalling and Communication in Kidney and Prostate Cancer', University of Strasbourg, Faculté de Médecine, 67085 Strasbourg, France.
    159INRS-Institut Armand-Frappier, 531 Boulevard des Prairies, Laval, QC H7V 1B7, Canada.
    160Department of Biology, Geology and Environmental Sciences, Alma Mater Studiorum Università di Bologna, Via Francesco Selmi, 3, 40126 Bologna, Italy, Center for Applied Biomedical Research, S. Orsola-Malpighi University Hospital, Via Massarenti, 9, 40126 Bologna, Italy, National Institute of Biostructures and Biosystems, Viale Medaglie d' Oro, 305, 00136 Roma, Italy.
    161Department of Biosciences and Veterinary Public Health, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, PO Box 7028, 75007 Uppsala, Sweden.
    162INSERM U1113, team 3 'Cell Signalling and Communication in Kidney and Prostate Cancer', University of Strasbourg, Faculté de Médecine, 67085 Strasbourg, France, Department of Cell and Developmental Biology, University of California, Irvine, CA 92697, USA.
    163Department of Biology/Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA 30314, USA.
    164Harvard Medical School/Brigham and Women's Hospital, Boston, MA 02115, USA.
    165United States Army Institute of Public Health, Toxicology Portfolio-Health Effects Research Program, Aberdeen Proving Ground, Edgewood, MD 21010-5403, USA.
    166Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC 27599, USA.
    167Department of Biosciences and Veterinary Public Health, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, PO Box 7028, 75007 Uppsala, Sweden.
    168Baylor College of Medicine, Houston, TX 77030, USA.
    169Environmental and Molecular Toxicology, Environmental Health Science Center, Oregon State University, Corvallis, OR 97331, USA.
    170Department of Pharmaceutical Sciences, West Virginia University, Morgantown, WV, 26506, USA.
    171Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kuwait University, PO Box 24923, Safat 13110, Kuwait and.
    172Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208, USA.
    173Department of Surgery, The Ohio State University College of Medicine, The James Comprehensive Cancer Center, Columbus, OH 43210, USA.
    Abstract

    Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.


    © The Author 2015. Published by Oxford University Press.

    Publikations ID: 26106142
    Quelle: öffnen
     
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