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 carot id artery injury in rats produced a marked inhibition of intimal hyper plasia and restenosis. The current study used smooth muscle cells (SMC ) in vitro to examine the radiation dose response and to investigate t he cellular mechanism by which radiation inhibits SMC proliferation. M ethods and Materials: Quiescent rat aortic SMC in plasma were refed wi th whole blood serum to stimulate synchronous proliferation and immedi ately irradiated with single fraction doses of 1.25-20 Gy. Results: Co mparison 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 S MC 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: R adiation likely inhibits SMC proliferation after arterial injury by a dose-dependent mechanism of lethal and/or sublethal cellular injury le ading to clonogenic cell death. Copyright (C) 1996 Elsevier Science In c.