Gamma radiation effect on vascular smooth muscle cells in culture

Purpose: Prior work in our laboratory demonstrated that external gamma irradiation administered within 48 h following balloon catheter carotid artery injury in rats produced a marked inhibition of intimal hyperplasia and restenosis. The current study used smooth muscle cells (SMC) in vitro to examine the radiation dose response and to investigate the cellular mechanism by which radiation inhibits SMC proliferation. Methods and Materials: Quiescent rat aortic SMC in plasma were refed with whole blood serum to stimulate synchronous proliferation and immediately irradiated with single fraction doses of 1.25-20 Gy. Results: Comparison between a micronucleus assay and a clonogenic assay indicated a dose-dependent inhibition of SMC growth, with an ED(50) at 2-3 Gy, The micronucleus assay also demonstrated a dose-dependent increase in apparent chromosomal damage at 72 h after irradiation, Inhibition of SMC growth by radiation did not correlate with changes in intracellular or released mitogenic activity, Furthermore, there was no evidence of apoptosis in irradiated SMC up to 96 h after treatment. Conclusion: Radiation likely inhibits SMC proliferation after arterial injury by a dose-dependent mechanism of lethal and/or sublethal cellular injury leading to clonogenic cell death. Copyright (C) 1996 Elsevier Science Inc.