DOSE-RESPONSE EFFECTS OF RADIATION ON THE PERMEABILITY OF ENDOTHELIAL-CELLS IN CULTURE

Increased permeability is an early and universal response of the vascu lature to radiation injury, yet the biological basis of this reaction is poorly understood. The present study determined the time course and the dose-response relationship of radiation-induced hyperpermeability in cultured bovine pulmonary artery endothelial (BPAE) cells. BPAE ce lls were grown to a confluent monolayer on microcarrier beads, and col umn chromatography methods were used to evaluate permeability to two l ow molecular weight compounds: sodium fluorescein (NaFlsc, mol. wt. = 342) and cyanocobalamin (B-12, mol. wt. = 1355). This is a novel in vi tro model to study mechanisms and modifiers of radiation-induced perme ability of endothelial cells under flow conditions using nonradioactiv e tracers. Cell-covered beads were exposed to a single dose of 10 Gy o f Cs-137 gamma rays and placed in the column, and permeability was mea sured every 30 min for 3 h. There was a time-dependent increase in per meability to both tracers, reaching significance by 2 h. Increased per meability was accompanied by perturbations in F-actin distribution in the BPAE cells as determined by rhodamine-phalloidin fluorescence micr oscopy. Neither catalase nor captopril ameliorated this hyperpermeabil ity, but dibutyryl cAMP partially prevented it. At 3 h after 0, 1, 2, 5 and 10 Gy irradiation, permeability values of 11.8 +/- 2.1, 13.9 +/- 2.2, 20.9 +/- 3.6, 24.8 +/- 2.8 and 27.2 +/- 3.3 (10(-5) cm/s, +/- SE M), respectively, were observed using NaFlsc. The increase was signifi cant (P < 0.05) at 2 Gy or higher. Permeability to B-12 was significan tly elevated after 5 or 10 Gy. These results suggest that permeability of endothelial cells to low molecular weight solutes increases within 3 h after therapeutic doses of radiation, and that cAMP ameliorates t his response. (C) 1996 by Radiation Research Society