Cigarette smoke and asbestos activate poly-ADP-ribose polymerase in alveolar epithelial cells

D. W. Kamp*, M. Srinivasan, S. A. Weitzman

*Corresponding author for this work

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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 tine 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.

Original languageEnglish (US)
Pages (from-to)68-76
Number of pages9
JournalJournal of Investigative Medicine
Volume49
Issue number1
DOIs
StatePublished - 2001

Keywords

  • Alveolar epithelial cells
  • Asbestos
  • Cigarette smoke
  • DNA damage
  • DNA repair
  • Lung injury
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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