Emilio Rojas, Amelia K Charles, Firouz Darroudi, Jordan Woodrick, Monica Vaccari, Laetitia Gonzalez, Carmel Mothersill, Amaya Azqueta, Roslida Abd Hamid, Hosni Salem, William H. Bisson, Adela Lopez de Cerain Salsamendi, Elizabeth P. Ryan, Chiara Mondello, Luoping Zhang, Luc Leyns, A. Ivana Scovassi, Stefano Forte, Gunnar Brunborg, Sofia Pavanello, Frederik J. van Schooten, Fahd Al-Mulla, Micheline Kirsch-Volders, Annamaria Colacci, Rabeah Al-Temaimi, Mahara Valverde, Amedeo Amedei, Patricia Ostrosky-Wegman, Dustin G. Brown, Jayadev Raju, Andrew Collins, Lorenzo Memeo, Tao Chen, Neetu Singh, Sabine A. S. Langie, Rabindra Roy, Lisbeth E. Knudsen, Nik van Larebeke, Ann-Karin Olsen, Daniel Desaulniers, Gudrun Koppen, Biology, Cell Genetics, Farmacologie en Toxicologie, and RS: NUTRIM - R4 - Gene-environment interaction
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 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.