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Causes of genome instability: the effect of low dose chemical exposures in modern society

Langie SA , Koppen G , Desaulniers D 1 , Al-Mulla F 2 , Al-Temaimi R 2 , Amedei A 3 Show all authors , Azqueta A 4 , Bisson WH 5 , Brown DG 6 , Brunborg G 7 , Charles AK 8 , Chen T 9 , Colacci A 10 , Darroudi F 11 , Forte S 12 , Gonzalez L 13 , Hamid RA 14 , Knudsen LE 15 , Leyns L 13 , Lopez de Cerain Salsamendi A 4 , Memeo L 12 , Mondello C 16 , Mothersill C 17 , Olsen AK 7 , Pavanello S 18 , Raju J 19 , Rojas E 20 , Roy R 21 , Ryan EP 6 , Ostrosky-Wegman P 20 , Salem HK 22 , Scovassi AI 16 , Singh N 23 , Vaccari M 10 , Van Schooten FJ 24 , Valverde M 20 , Woodrick J 21 , Zhang L 25 , van Larebeke N , Kirsch-Volders M 13 , Collins AR 26

Affiliations 

  • 1 Health Canada, Environmental Health Sciences and Research Bureau, Environmental Health Centre, Ottawa, Ontario K1A0K9, Canada
  • 2 Department of Pathology, Kuwait University, Safat 13110, Kuwait
  • 3 Department of Experimental and Clinical Medicine, University of Firenze, Florence 50134, Italy
  • 4 Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Navarra, Pamplona 31009, Spain
  • 5 Environmental and Molecular Toxicology, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331, USA
  • 6 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
  • 7 Department of Chemicals and Radiation, Division of Environmental Medicine, Norwegian Institute of Public Health, PO Box 4404, N-0403 Oslo, Norway
  • 8 Hopkins Building, School of Biological Sciences, University of Reading, Reading, Berkshire RG6 6UB, UK
  • 9 Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA
  • 10 Center for Environmental Carcinogenesis and Risk Assessment, Environmental Protection and Health Prevention Agency, Bologna 40126, Italy
  • 11 Human and Environmental Safety Research, Department of Health Sciences, College of North Atlantic, Doha, State of Qatar
  • 12 Mediterranean Institute of Oncology, 95029 Viagrande, Italy
  • 13 Laboratory for Cell Genetics, Vrije Universiteit Brussel, Brussels 1050, Belgium
  • 14 Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra, Serdang 43400, Selangor, Malaysia
  • 15 University of Copenhagen, Department of Public Health, Copenhagen 1353, Denmark
  • 16 Institute of Molecular Genetics, National Research Council, Pavia 27100, Italy
  • 17 Medical Physics & Applied Radiation Sciences, McMaster University, Hamilton, Ontario L8S4L8, Canada
  • 18 Department of Cardiac, Thoracic and Vascular Sciences, Unit of Occupational Medicine, University of Padova, Padova 35128, Italy
  • 19 Toxicology Research Division, Bureau of Chemical Safety Food Directorate, Health Products and Food Branch Health Canada, Ottawa, Ontario K1A0K9, Canada
  • 20 Departamento de Medicina Genomica y Toxicologia Ambiental, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de México, México CP 04510, México
  • 21 Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA
  • 22 Urology Department, kasr Al-Ainy School of Medicine, Cairo University, El Manial, Cairo 12515, Egypt
  • 23 Centre for Advanced Research, King George's Medical University, Chowk, Lucknow 226003, Uttar Pradesh, India
  • 24 Department of Toxicology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, 6200MD, PO Box 61, Maastricht, The Netherlands
  • 25 Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA 94720-7360, USA
  • 26 Department of Nutrition, University of Oslo, Oslo 0316, Norway
Carcinogenesis, 2015 Jun;36 Suppl 1:S61-88.
PMID: 26106144 DOI: 10.1093/carcin/bgv031

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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