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 language||English (US)|
|Journal||Journal of Investigative Medicine|
|State||Published - Jan 1 1996|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)