This Article Full Text Full Text (PDF) Supplementary Data All Versions of this Article: 0008-5472.CAN-08-2510v1 69/20/7917    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Gosselin, K. Articles by Abbadie, C. PubMed PubMed Citation Articles by Gosselin, K. Articles by Abbadie, C.

Senescence-Associated Oxidative DNA Damage Promotes the Generation of Neoplastic Cells

¹ Université Lille Nord de France; ² CNRS, UMR8161; ³ UDSL; ⁴ Institut Pasteur de Lille, Lille, France; ⁵ USTL; ⁶ CNRS, UMR3078, Villeneuve d'Ascq, France; ⁷ CEA Life Science Division, Fontenay-aux-Roses, France; ⁸ Laboratoire de Cytogénétique Erasme-ULB-CHU Brugmann, Brussels, Belgium; ⁹ CNRS, UMR5239, Faculté de Médecine Lyon Sud, Université Lyon 1, Pierre Bénite, France; ¹⁰ Institute of Pathology, University of Bonn, Bonn, Germany; ¹¹ Brunel Institute of Cancer Genetics and Pharmacogenomics, Brunel University, Uxbridge, Middlesex, United Kingdom

Requests for reprints: Corinne Abbadie, Institut de Biologie de Lille, 1 rue Calmette, BP 447, 59021 Lille Cedex, France. Phone: 33-3-20-87-11-02; Fax: 33-3-20-87-11-11; E-mail: corinne.abbadie{at}ibl.fr.

Key Words: oxidative stress • senescence • skin cancer

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. [Cancer Res 2009;69(20):7917–24]