Cigarette smoke extract induces DNA damage but not apoptosis in human bronchial epithelial cells.
Whether DNA damage caused by cigarette smoke leads to repair or apoptosis has not been fully elucidated. The current study demonstrates that cigarette smoke induces single-strand DNA damage in human bronchial epithelial cells. Cigarette smoke also stimulated caspase 3 precursors as well as intact poly (ADP-ribose) polymerase (PARP) production, but did not activate caspase 3 or cleave PARP, while the alkaloid camptothecin did so. Neither apoptosis nor necrosis was induced by cigarette smoke when the insult was removed within a designated time period. In contrast, DNA damage following cigarette smoke exposure was repaired as evidenced by decreasing terminal dUTP-biotin nick-end labeling positivity. The PARP inhibitor, 3-aminobenzamide blocked this repair. Furthermore, cells subjected to DNA damage were able to survive and proliferate clonogenically when changed to smoke-free conditions. These results suggest that cigarette smoke-induced DNA damage in bronchial epithelial cells is not necessarily lethal, and that PARP functions in the repair process. Our data also suggest that the potency of cigarettes as a carcinogen may result from their ability to induce DNA damage while failing to trigger the apoptotic progression permitting survival of cells harboring potentially oncogenic mutations.
Liu
Xiangde
X
University of Nebraska Medical Center, 985885 Nebraska Medical Center, Omaha, NE 68198-5885, USA.
Conner
Heather
H
Kobayashi
Tetsu
T
Kim
Huijung
H
Wen
Fuqiang
F
Abe
Shinji
S
Fang
Qiuhong
Q
Wang
Xingqi
X
Hashimoto
Mitsuyoshi
M
Bitterman
Peter
P
Rennard
Stephen I
SI
D017209:Apoptosis; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects / Q000235:genetics / Q000473:pathology; D014026:Nicotiana / Q000009:adverse effects*
D012906:Smoke; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases