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 cancer in asbestos workers. Although these carcinogens cause DNA damage to epithelial cells in vitro via generation of reactive oxygen species (ROS), it 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 asbestos, 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 rats were then evaluated in lungs using the terminal deoxynucleotidyl transferase (TDT)-mediated dUTP-biotin nick end labeling (TUNEL) method and by transmission electron microscopy (TEM). Increases in TUNEL-positive, necrotic epithelial cells occurred after exposure to asbestos alone and in an additive fashion after smoke and asbestos in combination. These results indicate that DNA strand breakage and necrosis are prominent mechanisms of injury by asbestos fibers and cigarette smoke in vivo to epithelial cells of the respiratory tract, thus validating in vitro observations from a number of laboratories.
Jung
M
M
Departments of Pathology, University of Vermont College of Medicine, Burlington, VT 05405, USA.
Davis
W P
WP
Taatjes
D J
DJ
Churg
A
A
Mossman
B T
BT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D017639:Asbestos, Amosite / Q000633:toxicity*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects*; D003043:Cocarcinogenesis; D004249:DNA Damage; D004357:Drug Synergism; D004847:Epithelial Cells / Q000737:chemistry / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D008297:Male; D009336:Necrosis; D010947:Plants, Toxic; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana
D017382:Reactive Oxygen Species; D012906:Smoke; D017639:Asbestos, Amosite