title: Cigarette smoke extract induces DNA damage but not apoptosis in human bronchial epithelial cells.
abstract: 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.
authors.affiliation: University of Nebraska Medical Center, 985885 Nebraska Medical Center, Omaha, NE 68198-5885, USA.
authors.forename: Xiangde
authors.initials: X
authors.lastname: Liu
authors.forename: Heather
authors.initials: H
authors.lastname: Conner
authors.forename: Tetsu
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Huijung
authors.initials: H
authors.lastname: Kim
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Wen
authors.forename: Shinji
authors.initials: S
authors.lastname: Abe
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Fang
authors.forename: Xingqi
authors.initials: X
authors.lastname: Wang
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Peter
authors.initials: P
authors.lastname: Bitterman
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Rennard
mesh_terms: 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*
chemical_list: D012906:Smoke; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases