Reoxygenation of hypoxic coronary smooth muscle cells amplifies growth-retarding effects of ionizing irradiation.

BACKGROUND Hypoxic human coronary smooth muscle cells (HCSMCs) are possible targets for brachytherapy to prevent restenosis after percutaneous transluminal coronary angiography. It is unclear whether growth kinetics and gene expression of these cells undergoing gamma-irradiation are changed by reoxygenation. METHODS AND RESULTS Hypoxic (H) and hypoxia-reoxygenated (H-R) HCSMCs were irradiated with gamma-radiation at single doses of 4, 8, and 16 Gy using a 60Co-source. Vascular endothelial growth factor gene expression of HCSMCs was dramatically suppressed in H-R versus H cells independent of the radiation dose (15+/-7% versus 2183+/-2023%, P<0.01, H-R versus H cells). An oxygen enhancement ratio of 1.8 was calculated after irradiation from the retarded growth of H-R versus hypoxic HCSMCs. Production of reactive oxygen species by HCSMCs after irradiation increased by 15+/-2% in H-R cells versus 7+/-1% in H cells (P<0.05). CONCLUSIONS Reoxygenation of hypoxic HCSMCs markedly amplifies growth-retarding effects of ionizing irradiation. On the basis of these findings, oxygenating radiosensitizers should be analyzed with regard to suitability for coronary brachytherapy to prevent restenosis.