title: Causes of genome instability: the effect of low dose chemical exposures in modern society.
abstract: Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis.
authors.affiliation: Environmental Risk and Health Unit, Flemish Institute for Technological Research (VITO), Boeretang 200, 2400 Mol, Belgium, Health Canada, Environmental Health Sciences and Research Bureau, Environmental Health Centre, Ottawa, Ontario K1A0K9, Canada, Department of Pathology, Kuwait University, Safat 13110, Kuwait, Department of Experimental and Clinical Medicine, University of Firenze, Florence 50134, Italy, Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Navarra, Pamplona 31009, Spain, Environmental and Molecular Toxicology, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331, USA, Department of Environmental and Radiological Health Sciences/Food Science and Human Nutrition, College of Veterinary Medicine and Biomedical Sciences, Colorado State University/Colorado School of Public Health, Fort Collins, CO 80523-1680, USA, Department of Chemicals and Radiation, Division of Environmental Medicine, Norwegian Institute of Public Health, PO Box 4404, N-0403 Oslo, Norway, Hopkins Building, School of Biological Sciences, University of Reading, Reading, Berkshire RG6 6UB, UK, Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA, Center for Environmental Carcinogenesis and Risk Assessment, Environmental Protection and Health Prevention Agency, Bologna 40126, Italy, Human and Environmental Safety Research, Department of Health Sciences, College of North Atlantic, Doha, State of Qatar, Mediterranean Institute of Oncology, 95029 Viagrande, Italy, Laboratory for Cell Genetics, Vrije Universiteit Brussel, Brussels 1050, Belgium, Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra, Serdang 43400, Selangor, Malaysia, University of Copenhagen, Department of Public Health, Copenhagen 1353, Denmark, Institute of Molecular Genetics, National Research Council, Pavia 27100, Italy, Medical Phys
authors.forename: Sabine A S
authors.initials: SA
authors.lastname: Langie
authors.affiliation: Environmental Risk and Health Unit, Flemish Institute for Technological Research (VITO), Boeretang 200, 2400 Mol, Belgium, Health Canada, Environmental Health Sciences and Research Bureau, Environmental Health Centre, Ottawa, Ontario K1A0K9, Canada, Department of Pathology, Kuwait University, Safat 13110, Kuwait, Department of Experimental and Clinical Medicine, University of Firenze, Florence 50134, Italy, Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Navarra, Pamplona 31009, Spain, Environmental and Molecular Toxicology, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331, USA, Department of Environmental and Radiological Health Sciences/Food Science and Human Nutrition, College of Veterinary Medicine and Biomedical Sciences, Colorado State University/Colorado School of Public Health, Fort Collins, CO 80523-1680, USA, Department of Chemicals and Radiation, Division of Environmental Medicine, Norwegian Institute of Public Health, PO Box 4404, N-0403 Oslo, Norway, Hopkins Building, School of Biological Sciences, University of Reading, Reading, Berkshire RG6 6UB, UK, Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA, Center for Environmental Carcinogenesis and Risk Assessment, Environmental Protection and Health Prevention Agency, Bologna 40126, Italy, Human and Environmental Safety Research, Department of Health Sciences, College of North Atlantic, Doha, State of Qatar, Mediterranean Institute of Oncology, 95029 Viagrande, Italy, Laboratory for Cell Genetics, Vrije Universiteit Brussel, Brussels 1050, Belgium, Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra, Serdang 43400, Selangor, Malaysia, University of Copenhagen, Department of Public Health, Copenhagen 1353, Denmark, Institute of Molecular Genetics, National Research Council, Pavia 27100, Italy, Medical Phys
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mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000139:chemically induced*; D002274:Carcinogens, Environmental / Q000009:adverse effects*; D004781:Environmental Exposure / Q000009:adverse effects*; D042822:Genomic Instability / Q000187:drug effects*; D015386:Hazardous Substances / Q000009:adverse effects*; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced* / Q000209:etiology*
chemical_list: D002274:Carcinogens, Environmental; D015386:Hazardous Substances