Apoptosis of Neural Precursor Cells following Gamma Irradiation is Modulated by Reactive Oxygen and Nitrogen Species (ROS/RNS).

ROBELLO E; DUBNER D; MICHELIN S; PÉREZ MR; PUNTARULO S; GISONE P

Buenos Aires

Congreso; 12th Biennial Meeting International Society for Free Radical Research; 2004

Enhanced radiation-induced generation of ROS/RNS has been observed after exposures to low radiation doses. This study was aimed to adress the participation of radiation-induced ROS, and endogenous NO generation in the radiation-induced apoptosis of neural cortical precursors. Cortical cells obtained from at 17 gestational day (gd) were irradiated with doses from 0,2 Gy to 2 Gy at a dose-rate of 0,3 Gy/m. A significant decrease of Luminol-dependent Chemiluminescence was observed in cells 30 min after irradiation, and basal levels at 120 min. Chemiluminescence in irradiated cells was significantly decreased by incubation with superoxide dismutase.Cellular NO content estimated as NO2- NO3- released to the culture medium, showed a significant increase in irradiated cells as compared to control values, up to 60 min post-irradiation. Apoptosis was evaluated by flow cytometry, morphology and DNA fragmentation after 24 h of irradiation. A significant increase was detected with 0,4 Gy doses. Pre-treatment of the cells with 10 mM N-acetyl cyteine (NAC), a precursor of intracellular GSH synthesis,lead to a significant decrease in cellular apoptosis, and inhibition of nitric oxide synthase (NOS) by L-NAME significantly increased apoptosis in irradiated cells. We conclude that a complex cross-talk between ROS and RNS play a pivotal role in the early signaling pathway leading to radiation-induced cell death.