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Disruptive chemicals, senescence and immortality

2015; Oxford University Press; Volume: 36; Issue: Suppl 1 Linguagem: Inglês

10.1093/carcin/bgv029

1460-2180

Amancio Carnero, Carmen Blanco‐Aparicio, Hiroshi Kondoh, Matilde E. Lleonart, Juan Fernando Martínez-Leal, Chiara Mondello, A. Ivana Scovassi, William H. Bisson, Amedeo Amedei, Rabindra Roy, Jordan Woodrick, Annamaria Colacci, Monica Vaccari, Jayadev Raju, Fahd Al‐Mulla, Rabeah Al‐Temaimi, Hosni Salem, Lorenzo Memeo, Stefano Forte, Neetu Singh, Roslida Abd Hamid, Elizabeth P. Ryan, Dustin G. Brown, John Pierce Wise, J. Wise, Hemad Yasaei,

Telomeres, Telomerase, and Senescence

Carcinogenesis is thought to be a multistep process, with clonal evolution playing a central role in the process. Clonal evolution involves the repeated 'selection and succession' of rare variant cells that acquire a growth advantage over the remaining cell population through the acquisition of 'driver mutations' enabling a selective advantage in a particular micro-environment. Clonal selection is the driving force behind tumorigenesis and possesses three basic requirements: (i) effective competitive proliferation of the variant clone when compared with its neighboring cells, (ii) acquisition of an indefinite capacity for self-renewal, and (iii) establishment of sufficiently high levels of genetic and epigenetic variability to permit the emergence of rare variants. However, several questions regarding the process of clonal evolution remain. Which cellular processes initiate carcinogenesis in the first place? To what extent are environmental carcinogens responsible for the initiation of clonal evolution? What are the roles of genotoxic and non-genotoxic carcinogens in carcinogenesis? What are the underlying mechanisms responsible for chemical carcinogen-induced cellular immortality? Here, we explore the possible mechanisms of cellular immortalization, the contribution of immortalization to tumorigenesis and the mechanisms by which chemical carcinogens may contribute to these processes.