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Disruptive chemicals, senescence and immortality.

Authors

Carnero A, Blanco-Aparicio C, Kondoh H, Lleonart ME, Martinez-Leal JF, Mondello C, Ivana Scovassi A, Bisson WH, Amedei A, Roy R, Woodrick J, Colacci A, Vaccari M, Raju J, Al-Mulla F, Al-Temaimi R, Salem HK, Memeo L, Forte S, Singh N, Hamid RA, Ryan EP, Brown DG, Wise JP Sr, Wise SS, Yasaei H.

Journal

CARCINOGENESIS 36(Suppl 1) S19-S37, 2015

CNR authors

MONDELLO, SCOVASSI

Modules

Abstract

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

Link to article

http://carcin.oxfordjournals.org/content/36/Suppl_1/S19.long

Keywords

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