Halothane-induced alterations in cellular structure and proliferation of A549 cells

Tissue Cell. 2008 Dec;40(6):397-404. doi: 10.1016/j.tice.2008.04.001. Epub 2008 Jun 3.


Genotoxicity, cytotoxicity or teratogenicity are among the well-known detrimental effects of the volatile anaesthetics. The aim of the present work was to study the structural changes, proliferative activity and the possibility of alveolar A549 cells to recover after in vitro exposure to halothane at 1.5 and 2.1mM concentrations. Our data indicated significant reduction of viability, suppression of mitotic activity more than 60%, and that these alterations were accompanied by disturbances of nuclear and nucleolar structures. The most prominent negative effect was the destruction of the lamellar bodies, the main storage organelles of pulmonary surfactant, substantial for the lung physiology. In conclusion, halothane applied at clinically relevant concentrations exerts genotoxic and cytotoxic effect on the alveolar cells in vitro, most likely as a consequence of stress-induced apoptosis, thus modulating the respiratory function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Inhalation / toxicity*
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Cell Nucleolus / drug effects
  • Cell Nucleolus / ultrastructure
  • Comet Assay
  • DNA Breaks, Double-Stranded / drug effects
  • Epithelial Cells / drug effects*
  • Epithelial Cells / pathology
  • Epithelial Cells / ultrastructure
  • Halothane / toxicity*
  • Humans
  • In Vitro Techniques
  • Lung Neoplasms
  • Microscopy, Electron
  • Mitosis / drug effects
  • Pulmonary Alveoli / cytology*
  • Pulmonary Surfactants / metabolism
  • Secretory Vesicles / drug effects
  • Secretory Vesicles / metabolism
  • Secretory Vesicles / ultrastructure


  • Anesthetics, Inhalation
  • Pulmonary Surfactants
  • Halothane