Cigarette smoke extract induces DNA damage but not apoptosis in human bronchial epithelial cells

Xiangde Liu, Heather Conner, Tetsu Kobayashi, Huijung Kim, Fuqiang Wen, Shinji Abe, Qiuhong Fang, Xingqi Wang, Mitsuyoshi Hashimoto, Peter Bitterman, Stephen I. Rennard

Research output: Contribution to journalArticle

82 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)121-129
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume33
Issue number2
DOIs
StatePublished - Aug 1 2005

Fingerprint

Smoke
Tobacco Products
DNA Damage
Epithelial Cells
Apoptosis
DNA
Poly(ADP-ribose) Polymerases
Repair
Caspase 3
Camptothecin
Biotin
Alkaloids
Carcinogens
Labeling
Cell Survival
Necrosis
Cells
Mutation

Keywords

  • Apoptosis
  • DNA content
  • PARP
  • TUNEL

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

Cigarette smoke extract induces DNA damage but not apoptosis in human bronchial epithelial cells. / Liu, Xiangde; Conner, Heather; Kobayashi, Tetsu; Kim, Huijung; Wen, Fuqiang; Abe, Shinji; Fang, Qiuhong; Wang, Xingqi; Hashimoto, Mitsuyoshi; Bitterman, Peter; Rennard, Stephen I.

In: American journal of respiratory cell and molecular biology, Vol. 33, No. 2, 01.08.2005, p. 121-129.

Research output: Contribution to journalArticle

Liu, X, Conner, H, Kobayashi, T, Kim, H, Wen, F, Abe, S, Fang, Q, Wang, X, Hashimoto, M, Bitterman, P & Rennard, SI 2005, 'Cigarette smoke extract induces DNA damage but not apoptosis in human bronchial epithelial cells', American journal of respiratory cell and molecular biology, vol. 33, no. 2, pp. 121-129. https://doi.org/10.1165/rcmb.2003-0341OC
Liu, Xiangde ; Conner, Heather ; Kobayashi, Tetsu ; Kim, Huijung ; Wen, Fuqiang ; Abe, Shinji ; Fang, Qiuhong ; Wang, Xingqi ; Hashimoto, Mitsuyoshi ; Bitterman, Peter ; Rennard, Stephen I. / Cigarette smoke extract induces DNA damage but not apoptosis in human bronchial epithelial cells. In: American journal of respiratory cell and molecular biology. 2005 ; Vol. 33, No. 2. pp. 121-129.
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