TY - JOUR
T1 - Causes of genome instability: the effect of low dose chemical exposures in modern society
AU - Langie, S.A.
AU - Koppen, G.
AU - Desaulniers, D.
AU - Al-Mulla, F.
AU - Al-Temaimi, R.
AU - Amedei, A.
AU - Azqueta, A.
AU - Bisson, W.H.
AU - Brown, D.G.
AU - Brunborg, G.
AU - Charles, A.K.
AU - Chen, T.
AU - Colacci, A.
AU - Darroudi, F.
AU - Forte, S.
AU - Gonzalez, L.
AU - Hamid, R.A.
AU - Knudsen, L.E.
AU - Leyns, L.
AU - Lopez de Cerain Salsamendi, A.
AU - Memeo, L.
AU - Mondello, C.
AU - Mothersill, C.
AU - Olsen, A.K.
AU - Pavanello, S.
AU - Raju, J.
AU - Rojas, E.
AU - Roy, R.
AU - Ryan, E.P.
AU - Ostrosky-Wegman, P.
AU - Salem, H.K.
AU - Scovassi, A.I.
AU - Singh, N.
AU - Vaccari, M.
AU - van Schooten, F.J.
AU - Valverde, M.
AU - Woodrick, J.
AU - Zhang, L.
AU - van Larebeke, N.
AU - Kirsch-Volders, M.
AU - Collins, A.R.
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 - TITANIUM-DIOXIDE NANOPARTICLES
KW - NUCLEOTIDE-EXCISION-REPAIR
KW - EPITHELIAL-MESENCHYMAL TRANSITION
KW - OXIDATIVE DNA-DAMAGE
KW - NF-KAPPA-B
KW - POLYCYCLIC AROMATIC-HYDROCARBONS
KW - MERCURY-INDUCED APOPTOSIS
KW - HYPOXIA-INDUCIBLE FACTOR
KW - AIR-POLLUTION EXPOSURE
KW - E-CADHERIN EXPRESSION
U2 - 10.1093/carcin/bgv031
DO - 10.1093/carcin/bgv031
M3 - Article
SN - 0143-3334
VL - 36
SP - S61-S88
JO - Carcinogenesis
JF - Carcinogenesis
ER -