title: Senescence-associated oxidative DNA damage promotes the generation of neoplastic cells.
abstract: Studies on human fibroblasts have led to viewing senescence as a barrier against tumorigenesis. Using keratinocytes, we show here that partially transformed and tumorigenic cells systematically and spontaneously emerge from senescent cultures. We show that these emerging cells are generated from senescent cells, which are still competent for replication, by an unusual budding-mitosis mechanism. We further present data implicating reactive oxygen species that accumulate during senescence as a potential mutagenic motor of this post-senescence emergence. We conclude that senescence and its associated oxidative stress could be a tumor-promoting state for epithelial cells, potentially explaining why the incidence of carcinogenesis dramatically increases with advanced age.
authors.affiliation: Université Lille Nord de France, CNRS, UMR8161, UDSL, Institut Pasteur de Lille, Lille, France.
authors.forename: Karo
authors.initials: K
authors.lastname: Gosselin
authors.forename: Sébastien
authors.initials: S
authors.lastname: Martien
authors.forename: Albin
authors.initials: A
authors.lastname: Pourtier
authors.forename: Chantal
authors.initials: C
authors.lastname: Vercamer
authors.forename: Peter
authors.initials: P
authors.lastname: Ostoich
authors.forename: Luc
authors.initials: L
authors.lastname: Morat
authors.forename: Laure
authors.initials: L
authors.lastname: Sabatier
authors.forename: Laurence
authors.initials: L
authors.lastname: Duprez
authors.forename: Claire
authors.initials: C
authors.lastname: T'kint de Roodenbeke
authors.forename: Eric
authors.initials: E
authors.lastname: Gilson
authors.forename: Nicolas
authors.initials: N
authors.lastname: Malaquin
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wernert
authors.forename: Predrag
authors.initials: P
authors.lastname: Slijepcevic
authors.forename: Marjan
authors.initials: M
authors.lastname: Ashtari
authors.forename: Fazia
authors.initials: F
authors.lastname: Chelli
authors.forename: Emeric
authors.initials: E
authors.lastname: Deruy
authors.forename: Bernard
authors.initials: B
authors.lastname: Vandenbunder
authors.forename: Yvan
authors.initials: Y
authors.lastname: De Launoit
authors.forename: Corinne
authors.initials: C
authors.lastname: Abbadie
mesh_terms: D000256:Adenoviridae; D000293:Adolescent; D000328:Adult; D020087:Alu Elements; D015153:Blotting, Western; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D016922:Cellular Senescence; D020552:Comet Assay; D004249:DNA Damage; D015342:DNA Probes; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006801:Humans; D017403:In Situ Hybridization; D007621:Karyotyping; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D055815:Young Adult
chemical_list: D015342:DNA Probes; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase