The potential for chemical mixtures from the environment to enable the cancer hallmark of sustained proliferative signalling
Wilhelm Engström 1, Philippa Darbre 2, Staffan Eriksson 3, Linda Gulliver 4, Tove Hultman 5, Michalis V Karamouzis 6, James E Klaunig 7, Rekha Mehta 8, Kim Moorwood 9, Thomas Sanderson 10, Hideko Sone 11, Pankaj Vadgama 12, Gerard Wagemaker 13, Andrew Ward 9, Neetu Singh 14, Fahd Al-Mulla 15, Rabeah Al-Temaimi 15, Amedeo Amedei 16, Anna Maria Colacci 17, Monica Vaccari 17, Chiara Mondello 18, A Ivana Scovassi 18, Jayadev Raju 19, Roslida A Hamid 20, Lorenzo Memeo 21, Stefano Forte 21, Rabindra Roy 22, Jordan Woodrick 22, Hosni K Salem 23, Elizabeth P Ryan 24, Dustin G Brown 24, William H Bisson 25
Affiliations
Affiliations
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.- 2School of Biological Sciences, University of Reading, Whiteknights, Reading RG6 6UB, UK.
- 3Department of Biochemistry, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Box 575, 75123 Uppsala, Sweden.
- 4Faculty of Medicine, University of Otago, PO Box 913, Dunedin 9050, New Zealand.
- 5Department 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.
- 6Department of Biological Chemistry Medical School, Institute of Molecular Medicine and Biomedical Research, University of Athens, Marasli 3, Kolonaki, Athens 10676, Greece.
- 7Department of Environmental Health, School of Public Health, Indiana University Bloomington , 1025 E. 7th Street, Suite 111, Bloomington, IN 47405, USA.
- 8Regulatory 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.
- 9Department of Biochemistry and Biology, University of Bath , Claverton Down, Bath BA2 7AY, UK.
- 10INRS-Institut Armand-Frappier, 531 boulevard des Prairies, Laval, Quebec H7V 1B7, Canada.
- 11Environmental Exposure Research Section, Center for Environmental Risk Research, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibraki 3058506, Japan.
- 12IRC in Biomedical Materials, School of Engineering & Materials Science, Queen Mary University of London, Mile End Road, London E1 4NS, UK.
- 13Center for Stem Cell Research and Development, Hacettepe University, Ankara 06100, Turkey.
- 14Centre for Advanced Research, King George's Medical University, Chowk, Lucknow, Uttar Pradesh 226003, India.
- 15Department of Pathology, Kuwait University, Safat 13110, Kuwait.
- 16Department of Experimental and Clinical Medicine, University of Firenze, Firenze 50134, Italy.
- 17Center for Environmental Carcinogenesis and Risk Assessment, Environmental Protection and Health Prevention Agency, Bologna 40126, Italy.
- 18Institute of Molecular Genetics, National Research Council, Pavia 27100, Italy.
- 19Regulatoty Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, HPFB, Health Canada, Ottawa, Ontario K1A0K9, Canada.
- 20Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
- 21Mediterranean Institute of Oncology, Viagrande 95029, Italy.
- 22Molecular Oncology Program, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
- 23Urology Dept. kasr Al-Ainy School of Medicine, Cairo University, El Manial, Cairo 12515, Egypt.
- 24Department of Environmental and Radiological Sciences, Colorado State University//Colorado School of Public Health, Fort Collins CO 80523-1680, USA and.
- 25Environmental and Molecular Toxicology, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331, USA.
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.
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