1. Senescence-associated oxidative DNA damage promotes the generation of neoplastic cells.
- Author
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Gosselin K, Martien S, Pourtier A, Vercamer C, Ostoich P, Morat L, Sabatier L, Duprez L, T'kint de Roodenbeke C, Gilson E, Malaquin N, Wernert N, Slijepcevic P, Ashtari M, Chelli F, Deruy E, Vandenbunder B, De Launoit Y, and Abbadie C
- Subjects
- Adenoviridae, Adolescent, Adult, Alu Elements, Blotting, Western, Cell Proliferation, Cells, Cultured, Comet Assay, DNA Probes, Epidermis metabolism, Epidermis pathology, Female, Fibroblasts metabolism, Fibroblasts pathology, Fluorescent Antibody Technique, Humans, In Situ Hybridization, Karyotyping, Keratinocytes metabolism, Keratinocytes pathology, Middle Aged, Neoplasms metabolism, Superoxide Dismutase metabolism, Young Adult, Cell Transformation, Neoplastic, Cellular Senescence, DNA Damage, Neoplasms pathology, Oxidative Stress, Reactive Oxygen Species metabolism
- 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.
- Published
- 2009
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