Cigarette smoke extract induces oxidative stress and apoptosis in human lung fibroblasts

Am J Physiol Lung Cell Mol Physiol. 2003 Jun;284(6):L955-63. doi: 10.1152/ajplung.00466.2001. Epub 2003 Jan 24.


Cigarette smoke is a mixture of chemicals having direct and/or indirect toxic effects on different lung cells. We investigated the effect of cigarette smoke on human lung fibroblasts (HFL-1) oxidation and apoptosis. Cells were exposed to various concentrations (1, 5, and 10%) of cigarette smoke extract (CSE) for 3 h, and oxidative stress and apoptosis were assessed by fluorescence-activated cell sorting and confocal laser fluorescence microscopy. Both oxidative stress and apoptosis exhibited a dose-response relationship with CSE concentrations. Lung fibroblasts also showed marked DNA fragmentation at the Comet assay after exposure to 10% CSE. Coincubation of HLF-1 cells with N-acetylcysteine (1 mM) during CSE exposure significantly reduced oxidative stress, apoptosis, and DNA fragmentation, whereas preincubation (3 h) with the glutathione-depleting agent buthionine sulfoximine (125 microM) produced a significant increase of oxidative stress. Cigarette smoke is a potent source of oxidative stress, DNA damage, and apoptosis for HFL-1 cells, and we speculate that this could contribute to the development of pulmonary emphysema in the lungs of smokers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Apoptosis / drug effects*
  • Benzimidazoles
  • Buthionine Sulfoximine / pharmacology
  • Comet Assay
  • DNA Damage
  • Enzyme Inhibitors / pharmacology
  • Fibroblasts / cytology*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Flow Cytometry
  • Fluorescent Dyes
  • Free Radical Scavengers / pharmacology
  • Glutathione / metabolism
  • Humans
  • Lung / cytology*
  • Microscopy, Confocal
  • Oxidative Stress / drug effects*
  • Smoking / adverse effects*


  • Benzimidazoles
  • Enzyme Inhibitors
  • Fluorescent Dyes
  • Free Radical Scavengers
  • Buthionine Sulfoximine
  • Glutathione
  • bisbenzimide ethoxide trihydrochloride
  • Acetylcysteine