The effect of norepinephrine on radiation sensitivity in rat ileal epithelial cells

Abstract

We previously reported that the apoptosis index in jejunal crypt cells was significantly greater in spontaneously hypertensive rats than in Wistar-Kyoto rats after X irradiation and that administration of reserpine to induce sympathetic dysfunction of spontaneously hypertensive rats or Wistar-Kyoto rats resulted in a significant suppression of apoptosis. We hypothesized that hyperfunction of the sympathetic nervous system is involved producing the high susceptibility to radiation-induced apoptosis of the jejunal crypt cells. To clarify this hypothesis, we examined the effect of norepinephrine (NE) on cell survival using the clonogenic assay and apoptosis after X-ray irradiation in rat ileal epithelial cells (IEC-18).
NE treatment in rat ileal epithelial cells resulted in the decrease of cell survival in a dose dependent manner (>1µM). A combination of NE 1µM and radiation decreased surviving fraction at 8 Gy from 24.1% to 6.4 % significantly. NE concentration 1µM resulted in increase the apoptotic rate from 3.5 % to 6.0 % 6 h after 8 Gy irradiation (p<0.05). The NE induced cell sensitivity to radiation was attenuated by alpha1-adrenergic antagonist (prazosin) but was not affected by beta-adrenergic antagonist (propranolol).
Our study suggested that NE enhanced sensitivity to radiation in rat epithelial cells and that may be caused through alpha adrenergic receptor.