title: Disruptive chemicals, senescence and immortality.
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.
authors.affiliation: Instituto de Biomedicina de Sevilla (IBIS/CSIC/HUVR/Univ. Sevilla), Oncohematology and Genetics Department, Avda Manuel siurot sn, 41013 Sevilla, Spain, Spanish National Cancer Research Center, Experimental Therapuetics Department, Melchor Fernandez Almagro, 3, 28029 Madrid, Spain, Department of Geriatric Medicine, Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-ku Kyoto 606-8507, Japan, Institut De Recerca Hospital Vall D'Hebron, Passeig Vall d'Hebron, 119-129, 08035 Barcelona, Spain, Cell Biology Department, Pharmamar-SAU, Avda. De los Reyes, 1, 28770-Colmenar Viejo, Madrid, Spain, Istituto di Genetica Molecolare, CNR, Via Abbiategrasso 207, 27100 Pavia, Italy, Environmental and Molecular Toxicology, Environmental Health Science Center, Oregon State University, Corvallis, OR 97331, USA, Department of Experimental and Clinical Medicine, University of Firenze, Italy, Florence 50134, Italy, Molecular Oncology Program, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA, Center for Environmental Carcinogenesis and Risk Assessment, Environmental Protection and Health Prevention Agency, Bologna 40126, Italy, Toxicology Research Division, Bureau of Chemical Safety Food Directorate, Health Products and Food Branch Health Canada, Ottawa, Ontario K1A0K9, Canada, Department of Pathology, Kuwait University, Safat 13110, Kuwait, Urology Department, kasr Al-Ainy School of Medicine, Cairo University, El Manial, Cairo 12515, Egypt, Mediterranean Institute of Oncology, Viagrande 95029, Italy, Centre for Advanced Research, King George's Medical University, Chowk, Lucknow, Uttar Pradesh 226003, India, Department of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor 43400, Malaysia, Department of Environmental and Radiological Health Sciences, Colorado State University/Colorado School of Public Health, Fort Collins, CO 80523-1680, USA, The Wise Laboratory of Environmental and Genetic Toxicology,
authors.forename: Amancio
authors.initials: A
authors.lastname: Carnero
authors.affiliation: Spanish National Cancer Research Center, Experimental Therapuetics Department, Melchor Fernandez Almagro, 3, 28029 Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Blanco-Aparicio
authors.affiliation: Department of Geriatric Medicine, Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-ku Kyoto 606-8507, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kondoh
authors.affiliation: Institut De Recerca Hospital Vall D'Hebron, Passeig Vall d'Hebron, 119-129, 08035 Barcelona, Spain.
authors.forename: Matilde E
authors.initials: ME
authors.lastname: Lleonart
authors.affiliation: Cell Biology Department, Pharmamar-SAU, Avda. De los Reyes, 1, 28770-Colmenar Viejo, Madrid, Spain.
authors.forename: Juan Fernando
authors.initials: JF
authors.lastname: Martinez-Leal
authors.affiliation: Istituto di Genetica Molecolare, CNR, Via Abbiategrasso 207, 27100 Pavia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Mondello
authors.affiliation: Istituto di Genetica Molecolare, CNR, Via Abbiategrasso 207, 27100 Pavia, Italy.
authors.forename: A Ivana
authors.initials: AI
authors.lastname: Scovassi
authors.affiliation: Environmental and Molecular Toxicology, Environmental Health Science Center, Oregon State University, Corvallis, OR 97331, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Bisson
authors.affiliation: Department of Experimental and Clinical Medicine, University of Firenze, Italy, Florence 50134, Italy.
authors.forename: Amedeo
authors.initials: A
authors.lastname: Amedei
authors.affiliation: Molecular Oncology Program, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
authors.forename: Rabindra
authors.initials: R
authors.lastname: Roy
authors.affiliation: Molecular Oncology Program, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Woodrick
authors.affiliation: Center for Environmental Carcinogenesis and Risk Assessment, Environmental Protection and Health Prevention Agency, Bologna 40126, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colacci
authors.affiliation: Center for Environmental Carcinogenesis and Risk Assessment, Environmental Protection and Health Prevention Agency, Bologna 40126, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Vaccari
authors.affiliation: Toxicology Research Division, Bureau of Chemical Safety Food Directorate, Health Products and Food Branch Health Canada, Ottawa, Ontario K1A0K9, Canada.
authors.forename: Jayadev
authors.initials: J
authors.lastname: Raju
authors.affiliation: Department of Pathology, Kuwait University, Safat 13110, Kuwait.
authors.forename: Fahd
authors.initials: F
authors.lastname: Al-Mulla
authors.affiliation: Department of Pathology, Kuwait University, Safat 13110, Kuwait.
authors.forename: Rabeah
authors.initials: R
authors.lastname: Al-Temaimi
authors.affiliation: Urology Department, kasr Al-Ainy School of Medicine, Cairo University, El Manial, Cairo 12515, Egypt.
authors.forename: Hosni K
authors.initials: HK
authors.lastname: Salem
authors.affiliation: Mediterranean Institute of Oncology, Viagrande 95029, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Memeo
authors.affiliation: Mediterranean Institute of Oncology, Viagrande 95029, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Forte
authors.affiliation: Centre for Advanced Research, King George's Medical University, Chowk, Lucknow, Uttar Pradesh 226003, India.
authors.forename: Neetu
authors.initials: N
authors.lastname: Singh
authors.affiliation: Department of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor 43400, Malaysia.
authors.forename: Roslida A
authors.initials: RA
authors.lastname: Hamid
authors.affiliation: Department of Environmental and Radiological Health Sciences, Colorado State University/Colorado School of Public Health, Fort Collins, CO 80523-1680, USA.
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Ryan
authors.affiliation: Department of Environmental and Radiological Health Sciences, Colorado State University/Colorado School of Public Health, Fort Collins, CO 80523-1680, USA.
authors.forename: Dustin G
authors.initials: DG
authors.lastname: Brown
authors.affiliation: The Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, Department of Applied Medical Sciences, University of Southern Maine, 96 Falmouth Street, Portland, ME 04104, USA and.
authors.forename: John Pierce
authors.initials: JP
authors.lastname: Wise
authors.affiliation: The Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, Department of Applied Medical Sciences, University of Southern Maine, 96 Falmouth Street, Portland, ME 04104, USA and.
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Wise
authors.affiliation: Brunel Institute of Cancer Genetics and Pharmacogenomics, Health and Environment Theme, Institute of Environment, Health and Societies, Brunel University London, Kingston Lane, Uxbridge, UB8 3PH, UK.
authors.forename: Hemad
authors.initials: H
authors.lastname: Yasaei
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000139:chemically induced*; D002273:Carcinogens / Q000008:administration & dosage*; D016922:Cellular Senescence / Q000187:drug effects*; D004781:Environmental Exposure / Q000009:adverse effects; D015386:Hazardous Substances / Q000009:adverse effects*; D006801:Humans
chemical_list: D002273:Carcinogens; D015386:Hazardous Substances