title: The potential for chemical mixtures from the environment to enable the cancer hallmark of sustained proliferative signalling.
abstract: The aim of this work is to review current knowledge relating the established cancer hallmark, sustained cell proliferation to the existence of chemicals present as low dose mixtures in the environment. Normal cell proliferation is under tight control, i.e. cells respond to a signal to proliferate, and although most cells continue to proliferate into adult life, the multiplication ceases once the stimulatory signal disappears or if the cells are exposed to growth inhibitory signals. Under such circumstances, normal cells remain quiescent until they are stimulated to resume further proliferation. In contrast, tumour cells are unable to halt proliferation, either when subjected to growth inhibitory signals or in the absence of growth stimulatory signals. Environmental chemicals with carcinogenic potential may cause sustained cell proliferation by interfering with some cell proliferation control mechanisms committing cells to an indefinite proliferative span.
authors.affiliation: Department of Biosciences and Veterinary Public Health, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, PO Box 7028, 75007 Uppsala, Sweden, wilhelm.engstrom@slu.se.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Engström
authors.affiliation: School of Biological Sciences, University of Reading, Whiteknights, Reading RG6 6UB, UK.
authors.forename: Philippa
authors.initials: P
authors.lastname: Darbre
authors.affiliation: Department of Biochemistry, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Box 575, 75123 Uppsala, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Eriksson
authors.affiliation: Faculty of Medicine, University of Otago, PO Box 913, Dunedin 9050, New Zealand.
authors.forename: Linda
authors.initials: L
authors.lastname: Gulliver
authors.affiliation: Department of Biosciences and Veterinary Public Health, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, PO Box 7028, 75007 Uppsala, Sweden, School of Biological Sciences, University of Reading, Whiteknights, Reading RG6 6UB, UK.
authors.forename: Tove
authors.initials: T
authors.lastname: Hultman
authors.affiliation: Department of Biological Chemistry Medical School, Institute of Molecular Medicine and Biomedical Research, University of Athens, Marasli 3, Kolonaki, Athens 10676, Greece.
authors.forename: Michalis V
authors.initials: MV
authors.lastname: Karamouzis
authors.affiliation: Department of Environmental Health, School of Public Health, Indiana University Bloomington , 1025 E. 7th Street, Suite 111, Bloomington, IN 47405, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Klaunig
authors.affiliation: Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, HPFB, Health Canada, 251 Sir F.G. Banting Driveway, AL # 2202C, Tunney's Pasture, Ottawa, Ontario K1A 0K9, Canada.
authors.forename: Rekha
authors.initials: R
authors.lastname: Mehta
authors.affiliation: Department of Biochemistry and Biology, University of Bath , Claverton Down, Bath BA2 7AY, UK.
authors.forename: Kim
authors.initials: K
authors.lastname: Moorwood
authors.affiliation: INRS-Institut Armand-Frappier, 531 boulevard des Prairies, Laval, Quebec H7V 1B7, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Sanderson
authors.affiliation: Environmental Exposure Research Section, Center for Environmental Risk Research, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibraki 3058506, Japan.
authors.forename: Hideko
authors.initials: H
authors.lastname: Sone
authors.affiliation: IRC in Biomedical Materials, School of Engineering & Materials Science, Queen Mary University of London, Mile End Road, London E1 4NS, UK.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Vadgama
authors.affiliation: Center for Stem Cell Research and Development, Hacettepe University, Ankara 06100, Turkey.
authors.forename: Gerard
authors.initials: G
authors.lastname: Wagemaker
authors.affiliation: Department of Biochemistry and Biology, University of Bath , Claverton Down, Bath BA2 7AY, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Ward
authors.affiliation: Centre for Advanced Research, King George's Medical University, Chowk, Lucknow, Uttar Pradesh 226003, India.
authors.forename: Neetu
authors.initials: N
authors.lastname: Singh
authors.affiliation: Department of Pathology, Kuwait University, Safat 13110, Kuwait.
authors.forename: Fahd
authors.initials: F
authors.lastname: Al-Mulla
authors.affiliation: Department of Pathology, Kuwait University, Safat 13110, Kuwait.
authors.forename: Rabeah
authors.initials: R
authors.lastname: Al-Temaimi
authors.affiliation: Department of Experimental and Clinical Medicine, University of Firenze, Firenze 50134, Italy.
authors.forename: Amedeo
authors.initials: A
authors.lastname: Amedei
authors.affiliation: Center for Environmental Carcinogenesis and Risk Assessment, Environmental Protection and Health Prevention Agency, Bologna 40126, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Colacci
authors.affiliation: Center for Environmental Carcinogenesis and Risk Assessment, Environmental Protection and Health Prevention Agency, Bologna 40126, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Vaccari
authors.affiliation: Institute of Molecular Genetics, National Research Council, Pavia 27100, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Mondello
authors.affiliation: Institute of Molecular Genetics, National Research Council, Pavia 27100, Italy.
authors.forename: A Ivana
authors.initials: AI
authors.lastname: Scovassi
authors.affiliation: Regulatoty Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, HPFB, Health Canada, Ottawa, Ontario K1A0K9, Canada.
authors.forename: Jayadev
authors.initials: J
authors.lastname: Raju
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors.forename: Roslida A
authors.initials: RA
authors.lastname: Hamid
authors.affiliation: Mediterranean Institute of Oncology, Viagrande 95029, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Memeo
authors.affiliation: Mediterranean Institute of Oncology, Viagrande 95029, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Forte
authors.affiliation: Molecular Oncology Program, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
authors.forename: Rabindra
authors.initials: R
authors.lastname: Roy
authors.affiliation: Molecular Oncology Program, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Woodrick
authors.affiliation: Urology Dept. kasr Al-Ainy School of Medicine, Cairo University, El Manial, Cairo 12515, Egypt.
authors.forename: Hosni K
authors.initials: HK
authors.lastname: Salem
authors.affiliation: Department of Environmental and Radiological Sciences, Colorado State University//Colorado School of Public Health, Fort Collins CO 80523-1680, USA and.
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Ryan
authors.affiliation: Department of Environmental and Radiological Sciences, Colorado State University//Colorado School of Public Health, Fort Collins CO 80523-1680, USA and.
authors.forename: Dustin G
authors.initials: DG
authors.lastname: Brown
authors.affiliation: Environmental and Molecular Toxicology, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Bisson
mesh_terms: D000818:Animals; D002274:Carcinogens, Environmental / Q000009:adverse effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004781:Environmental Exposure / Q000009:adverse effects*; D015386:Hazardous Substances / Q000009:adverse effects*; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced* / Q000209:etiology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002274:Carcinogens, Environmental; D015386:Hazardous Substances