ARTÍCULO

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

Autores: Langie, S.A.S.; Koppen, G. (Autor de correspondencia); Desaulniers, D.; Al-Mulla, F.; Al-Temaimi, R.; Amedei, A.; Azqueta Oscoz, Amaya; Bisson, W. H.; Brown, D.; Brunborg, G.; Charles, A. K.; Chen, T.; Colacci, A.; Darroudi, F.; Forte, S.; Gonzalez, L.; Hamid, R. A.; Knudsen, L. E.; Leyns, L.; López de Cerain Salsamendi, Adela; Memeo, L.; Mondello, C.; Mothersill, C.; Olsen, A. K.; Pavanello, S.; Raju, J.; Rojas, E.; Roy, R.; Ryan, E.; Ostrosky-Wegman, P.; Salem, H. K.; Scovassi, I.; Singh, N.; Vaccari, M.; Van Schooten, F. J.; Valverde, M.; Woodrick, J.; Zhang, L.; van Larebeke, N.; Kirsch-Volders, M.; Collins, A. R.
Título de la revista: CARCINOGENESIS
ISSN: 0143-3334
Volumen: 36
Número: Supl. 1
Páginas: S61 - S88
Fecha de publicación: 2015
Resumen:
In this review, we focus on some 'chemical disruptors' and how they add to the burden of genome instability, thereby increasing cancer incidence risk.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 out