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Cigarette Smoke and Asbestos Activate Poly-ADP-Ribose Polymerase in Alveolar Epithelial Cells
  1. David W. Kamp,
  2. Malathi Srinivasan,
  3. Sigmund A. Weitzman
  1. From the Department of Medicine, Divisions of Pulmonary and Critical Care Medicine and Hematology-Oncology, Veterans Affairs Chicago Health Care System-Lakeside Division and Northwestern University Medical School, Chicago, Ill
  1. Address correspondence to: David W. Kamp, MD, Northwestern University Medical School, Pulmonary and Critical Care Medicine, 300 East Superior Street, Tarry-Room 14-707, Chicago, IL 60611. d-kamp{at}


Background Cigarette smoke augments asbestos-induced bronchogenic carcinoma in a synergistic manner by mechanisms that are not established. One important mechanism may involve alveolar epithelial cell (AEC) injury resulting from oxidant-induced DNA damage that subsequently activates poly (ADP-ribose) polymerase (PARP), an enzyme involved in DNA repair that can deplete cellular energy stores. We previously showed that whole aqueous cigarette smoke extracts (CSE) augment amosite asbestos-induced DNA damage and cytotoxicity to cultured AEC in part by generating iron-induced free radicals. We hypothesized that CSE increase asbestos-induced AEC injury by triggering PARP activation resulting from DNA damage caused by iron-induced free radicals.

Methods Aqueous CSE were prepared fresh on the day of each experiment. PARP activity in WI-26 (a type I-like cell line) and A549 (a type II-like cell line) cells was assessed by the uptake of labeled NAD over 4 hours and confirmed on the basis of the reduction of PARP levels in the presence of a PARP inhibitor, 3-aminobenzamide (3-ABA). Cell survival was assessed by trypan blue dye exclusion.

Results Hydrogen peroxide (H2O2; 1-250 μM), CSE (0.4-10 vol%), and amosite asbestos (5-250 μg/cm2) each caused PARP activation in WI-26 and A549 cells. The combination of asbestos (5 μg/cm2) and CSE (0.04-10%) induced WI-26 and A549 cell PARP activation without evidence of synergism. 3-ABA significantly attenuated WI-26 and A549 cell PARP activity and cell death after exposure to H2O2, CSE, and asbestos. Phytic acid, an iron chelator, catalase, and superoxide dismutase each decreased WI-26 cell PARP activation caused by asbestos and CSE.

Conclusions CSE and asbestos induce PARP activation in cultured AEC in a nonsynergistic manner. These data provide further support that asbestos and cigarette smoke are genotoxic to relevant lung target cells and that iron-induced free radicals in part cause these effects.

Key Words:
  • asbestos
  • cigarette smoke
  • alveolar epithelial cells
  • DNA damage
  • reactive oxygen species
  • lung injury
  • DNA repair

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