A Role for Fibroblasts in Mediating the Effects of Tobacco-Induced Epithelial Cell Growth and Invasion
A Role for Fibroblasts in Mediating the Effects of Tobacco-Induced Epithelial Cell Growth and Invasion Jean-Philippe Coppe,1 Megan Boysen,2 Chung Ho Sun,2 Brian J.F. Wong,2 Mo K. Kang,3 No-Hee Park,3 Pierre-Yves Desprez,1 Judith Campisi,1 and Ana Krtolica1 1Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California; 2University of California Irvine, Irvine, California; and 3School of Dentistry, Center for the Health Sciences, University of California Los Angeles, Los Angeles, California Abstract Introduction Cigarette smoke and smokeless tobacco extracts Approximately one-third of cancer deaths in the United contain multiple carcinogenic compounds,but little States are directly linked to tobacco use, and an unknown is known about the mechanisms by which tumors additional number of cancers are linked to environmental develop and progress upon chronic exposure to carcinogens in general. In the case of tobacco use, cigarette carcinogens such as those present in tobacco smoke has been identified as the major cause of cancers of the products. Here,we examine the effects of smokeless lung, oral cavity, larynx, and esophagus. Moreover, smokeless tobacco extracts on human oral fibroblasts. We show tobacco use has been linked primarily to oral cavity cancers, that smokeless tobacco extracts elevated the levels of particularly cancers of the cheek and gum (1, 2). intracellular reactive oxygen,oxidative DNA damage, Cell culture, animal, and human studies indicate that and DNA double-strand breaks in a dose-dependent reactive oxygen species (ROS) and oxidative DNA damage manner. Extended exposure to extracts induced are critical for the pathologies induced by tobacco and other fibroblasts to undergo a senescence-like growth arrest, environmental carcinogens (3-6).
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