Radiation reduces cyclooxygenase activity in cultured human endothelial cells at low doses.
The effect of radiation on prostaglandin (PG) production was investigated in cultured human umbilical vein endothelial cells. It was found that 48 hours after irradiation the endothelial cell capacity to synthesize prostacyclin (PGI2), Prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) from exogenous arachidonic acid (AA) was strongly reduced in a radiation dose-dependent way, with 50% of the maximal inhibition at approximately 2 Gy. By incubating the endothelial cells between 24 and 48 hours after irradiation with 50 U/ml interleukin-2 (IL-2), which is known to selectively stimulate de novo synthesis of cyclooxygenase, the PGI2 synthesis from exogenous AA was nearly completely restored. Basal PGI2 release was not influenced by radiation (up to 25 Gy), nor was there increased cell damage as measured by LDH release during 72 hours after irradiation compared with controls. Clonogenic cell survival after irradiation showed a typical exponential radiation dose-response curve with a fairly broad initial shoulder. The data presented in this study suggest that the reduction of endothelial PGI2 synthesis after low doses of radiation is primarily due to a reduction in the activity of the enzyme cyclooxygenase.
Verheij
M
M
Department of Radiotherapy, The Netherlands Cancer Institute (Antoni van Leeuwenhoek Huis), Amsterdam.
Koomen
G C
GC
van Mourik
J A
JA
Dewit
L
L
D016718:Arachidonic Acid / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D015237:Dinoprost / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D004307:Dose-Response Relationship, Radiation; D004730:Endothelium, Vascular / Q000201:enzymology / Q000528:radiation effects*; D011464:Epoprostenol / Q000096:biosynthesis; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism / Q000528:radiation effects*; D014471:Umbilical Veins
D007376:Interleukin-2; D016718:Arachidonic Acid; D015237:Dinoprost; D011464:Epoprostenol; D007770:L-Lactate Dehydrogenase; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone