Asbestos and cigarette smoke cause increased DNA strand breaks and necrosis in bronchiolar epithelial cells in vivo

Coexposures to asbestos and cigarette smoke cause increased risks of lung c ancer in asbestos workers. Although these carcinogens cause DNA damage to e pithelial cells in vitro via generation of reactive oxygen species (ROS), i t is unclear whether they cause injury to bronchiolar epithelial cells (i.e ., the target cells of lung cancers in vivo). We exposed rats to amosite as bestos, cigarette smoke, and the two agents in combination for 1, 2, and 14 d. Numbers of cells exhibiting DNA strand breaks in comparison to sham rat s were then evaluated in lungs using the terminal deoxynucleotidyl transfer ase (TDT)-mediated dUTP-biotin nick end labeling (TUNEL) method and by tran smission electron microscopy (TEM). Increases in TUNEL-positive, necrotic e pithelial cells occurred after exposure to asbestos alone and in an additiv e fashion after smoke and asbestos in combination. These results indicate t hat DNA strand breakage and necrosis are prominent mechanisms of injury by asbestos fibers and cigarette smoke in vivo to epithelial cells of the resp iratory tract, thus validating in vitro observations from a number of labor atories. (C) 2000 Elsevier Science Inc.