TY - JOUR

T1 - Causes of genome instability

T2 - the effect of low dose chemical exposures in modern society

AU - Langie, Sabine A S

AU - Koppen, Gudrun

AU - Desaulniers, Daniel

AU - Al-Mulla, Fahd

AU - Al-Temaimi, Rabeah

AU - Amedei, Amedeo

AU - Azqueta, Amaya

AU - Bisson, William H

AU - Brown, Dustin G

AU - Brunborg, Gunnar

AU - Charles, Amelia K

AU - Chen, Tao

AU - Colacci, Annamaria

AU - Darroudi, Firouz

AU - Forte, Stefano

AU - Gonzalez, Laetitia

AU - Hamid, Roslida A

AU - Knudsen, Lisbeth E

AU - Leyns, Luc

AU - Lopez de Cerain Salsamendi, Adela

AU - Memeo, Lorenzo

AU - Mondello, Chiara

AU - Mothersill, Carmel

AU - Olsen, Ann-Karin

AU - Pavanello, Sofia

AU - Raju, Jayadev

AU - Rojas, Emilio

AU - Roy, Rabindra

AU - Ryan, Elizabeth P

AU - Ostrosky-Wegman, Patricia

AU - Salem, Hosni K

AU - Scovassi, A Ivana

AU - Singh, Neetu

AU - Vaccari, Monica

AU - Van Schooten, Frederik J

AU - Valverde, Mahara

AU - Woodrick, Jordan

AU - Zhang, Luoping

AU - van Larebeke, Nik

AU - Kirsch-Volders, Micheline

AU - Collins, Andrew R

N1 - © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PY - 2015/6

Y1 - 2015/6

N2 - 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.

AB - 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.

KW - Animals

KW - Carcinogenesis

KW - Carcinogens, Environmental

KW - Environmental Exposure

KW - Genomic Instability

KW - Hazardous Substances

KW - Humans

KW - Neoplasms

U2 - 10.1093/carcin/bgv031

DO - 10.1093/carcin/bgv031

M3 - Review

C2 - 26106144

VL - 36

SP - S61-S88

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - Supplement 1

ER -