The effect of radiation on prostacyclin (PGI2) production by cultured endothelial cells.

The effect of ionizing irradiation on the synthesis of prostacyclin (PGI2) by cultured bovine aortic endothelial cells was determined. PGI2 was measured in the culture medium by a radioimmunoassay for 6-Keto PGF1 alpha. Two phenomena were observed following irradiation: a) Cells which suffered an immediate radiation damage (1000-5000 rads) released high quantities of PGI2 to the culture medium. This was due to a de novo synthesis of PGI2 stimulated by radiation induced cellular damage, since pretreatment with aspirin of the endothelial cell monolayers resulted in a marked inhibition of PGI2 release following irradiation. b) Metabolically active cells which remained confluent and firmly attached to the culture dish following single, low and intermediate doses (200-1200 rads) radiation, exhibited a marked decrease in their capacity to synthesize PGI2 upon exposure to various stimuli of the arachidonic acid cascade (arachidonic acid, melittin, ionophore A23187 and PGH2). Similar results were observed with cells treated with fractionated radiation. The quantities of PGI2 produced by the endothelial cells decreased as a function of the dose of radiation and time interval between irradiation and subsequent stimulation. Radiation had a minimal effect on the nonthrombogenic properties of the endothelial cells, as evidenced by the small increase in platelet adherence to the endothelial cells. The effect of radiation on PGI2 production by the vascular endothelium may be relevant to the development of radiation induced capillary occlusions, and the enhancement of atherosclerotic lesions in large vessels.