A549 subclones demonstrate heterogeneity in toxicological sensitivity and antioxidant profile

Nobuo Watanabe, Dale A. Dickinson, David M. Krzywanski, Karen E. Iles, Hongqiao Zhang, Charles J. Venglarik, Henry Jay Forman

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

In A549 cell culture, significant variability was found in sensitivity to actinomycin D. Using limiting dilution, actinomycin D-susceptible (G4S) and -resistant (D3R) subclones were isolated. G4S cells were also susceptible to protein synthesis inhibitors, a redox cycling quinone, and an electrophile with concomitant activation of caspases 3 and 9. D3R cells were resistant to these agents without caspase activation. Antioxidant profiles revealed that D3R cells had significantly higher glutathione and glutathione reductase activity but markedly lower catalase, glutathione peroxidase, and aldehyde reductase activities than G4S cells. Thus A549 cells contain at least two distinct subpopulations with respect to predisposition to cell death and antioxidant profile. Because sensitivities to agents and the antioxidant profile were inconsistent, mechanisms independent of antioxidants, including the apparent inability to activate caspases in D3R cells, may play an important role. Regardless, the results suggest that antioxidant profiles of asymmetrical cell populations cannot predict sensitivity to oxidants and warn that the use of single subclones is advisable for mechanistic studies using A549 or other unstable cell lines.

Original languageEnglish
Pages (from-to)L726-L736
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume283
Issue number4 27-4
DOIs
Publication statusPublished - 2002 Oct

Keywords

  • Apoptosis
  • Caspase
  • Enzyme
  • Genetic instability
  • Oxidative stress

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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