Keratinocvte growth factor (kgf) reduces radiation-induced dna damage in alveolar epithelial cells

M. Takeoka*, W. F. Ward, N. Pollack, David William Kamp, R. J. Panos

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

KGF is a mesenchymal cell-derived heparin-binding growth factor that is mitogenic for epithelial cells. Within the lung, intratracheal instillation of KGF stimulates alveolar epithelial cell proliferation and ameliorates hyperoxia-induced lung damage in the rat. KGF also attenuates hydrogen peroxide-induced DNA damage in cultured alveolar epithelial cells. Because radiation-induced alveolar injury is caused in part by epithelial cell DNA damage, we determined if KGF reduced DNA strand breaks in irradiated A549 epithelial cells. KGF (0-100 ng/ml) was added to subconfluent A549 cells for 24 h; the cells were washed and exposed to Cs gamma rays at a dose rate of 1 Gy/min at room temperature. DNA damage was measured by alkaline unwinding and ethidium bromide fluorescence 30 min later. Irradiation caused a dose-dependent increase in DNA strand breaks. After a dose of 30 Gy, KGF caused a dose-dependent reduction in A549 cell DNA damage: DNA Damage (% double stranded DNA) KGF (ng/ml) 0 1 10 20 100 0 Gy 90.2±4.6 86.4±2.9 85.5±3.8 81.5±5.1 85.2±3.9 30 Gy 44.6±3.5 47.3±5.7 57.7±6.5± 58.4±5.9 61.6±5.0 [mean±SE, n=6; p<0.05 compared with KGF 0 ng/ml] No reduction in DNA damage occurred when the cells were maintained at 4°C during irradiation and the 30 min recovery period. Thus, KGF causes a dose-dependent reduction in radiation-induced A549 alveolar epithelial cell DNA damage and this effect appears to be due to accelerated repair of DNA strand breaks.

Original languageEnglish (US)
JournalJournal of Investigative Medicine
Volume44
Issue number3
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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