Recovery of prostacyclin capacity of irradiated endothelial cells and the protective effect of vitamin C.
Ionizing irradiation has been reported to affect prostacyclin (PGI2) production by intact blood vessels and cultured endothelial cells (EC) due to damage of enzymes of the arachidonate cascade. In the present study, we investigated whether EC can recover from radiation injury and regain their capacity to produce PGI2. Bovine aortic EC were exposed to radiation doses of 3 and 6 Gy and their capacity to produce PGI2 in response to stimulation with arachidonic acid was tested, at various times after irradiation. The results of these experiments showed clearly that EC exposed to single or fractionated irradiation could recover their capacity to produce PGI2 depending on the radiation dose and the time period following radiation. Radiation damage is associated with oxidant stress and the production of free radicals. We therefore tested the ability of an oxygen radical scavenger, vitamin C, to protect the capacity of irradiated EC to produce PGI2. Pretreatment of EC with low concentrations of vitamin C inhibited the radiation induced release of PGI2 to the culture medium. Vitamin C also enhanced the capacity of irradiated EC to produce PGI2 following short stimulation with arachidonic acid. Treatment with this scavenger however, did not protect the cells against the cytopathic effects of radiation.
Eldor
A
A
Department of Hematology, Hadassah University Hospital, Jerusalem, Israel.
Vlodavsky
I
I
Riklis
E
E
Fuks
Z
Z
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D001205:Ascorbic Acid / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D011464:Epoprostenol / Q000096:biosynthesis*; D066298:In Vitro Techniques; D011833:Radiation Injuries, Experimental / Q000378:metabolism
D011464:Epoprostenol; D001205:Ascorbic Acid