KGF facilitates repair of radiation-induced DNA damage in alveolar epithelial cells

Michiko Takeoka, William F. Ward, Haunani Pollack, David W. Kamp, Ralph J. Panos*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

Administration of exogenous keratinocyte growth factor (KGF) prevents or attenuates several forms of oxidant-mediated lung injury. Because DNA damage in epithelial cells is a component of radiation pneumotoxicity, we determined whether KGF ameliorated DNA strand breaks in irradiated A549 cells. Cells were exposed to 137Cs gamma rays, and DNA damage was measured by alkaline unwinding and ethidium bromide fluorescence after a 30-min recovery period. Radiation induced a dose-dependent increase in DNA strand breaks. The percentage of double-stranded DNA after exposure to 30 Gy increased from 44.6 ± 3.5% in untreated control cells to 61.6 ± 5.0% in cells cultured with 100 ng/m) KGF for 24 h (P < 0.05). No reduction in DNA damage occurred when the cells were cultured with KGF but maintained at 0°C during and after irradiation. The sparing effect of KGF on radiation-induced DNA damage was blocked by aphidicolin, an inhibitor of DNA polymerases-α, -δ, and -ε and by butylphenyl dGTP, which blocks DNA polymerase-α strongly and polymerases- δ and -ε less effectively. However, dideoxythymidine triphosphate, a specific inhibitor of DNA polymerase-β, did not abrogate the KGF effect. Thus KGF increases DNA repair capacity in irradiated pulmonary epithelial cells, an effect mediated at least in part by DNA polymerases-α, -δ, and - ε. Enhancement of DNA repair capability after cell damage may be one mechanism by which KGF is able to ameliorate oxidant-mediated alveolar epithelial injury.

Original languageEnglish (US)
Pages (from-to)L1174-L1180
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume272
Issue number6 16-6
DOIs
StatePublished - Jun 1997

Keywords

  • Alveolar epithelium
  • Keratinocyte growth factor

ASJC Scopus subject areas

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

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