Early radiation induced metabolic changes in cultured vascular endothelial cells

To investigate early radiation induced changes in vessel wall function, the author's used cultures of bovine aortic endothelial cells (BAEC), which produce and rest in vitro on an underlying basement membrane (BM) and maintain other in vivo phenotyic characteristics of BAEC. When dissociated from the BM, the radiation dose survival curve showed a Do of 145 cGy and n = 2.5. When confluent plateau phase cells resting on the BM were irradiated (2-20 CGy) 20-60% of the cells detached from the BM, and the remaining metabolically active cells, which were still adherent to the BM, exhibited a marked decrease in the capacity to synthesize prostacyclin (PGI/sub 2/). This injury to enzymes involved in the arachidonic acid cascade spontaneously recovered following low doses of radiation, and was significantly reduced when radiation was delivered in the presence of ascorbic acid. Irradiated BAEC also procduced and released a chemotactic lipid demonstrated by using human neutrophils in Boyden Chambers, inhibited by preincubation with a lipoxygenase inhibitor. The authors also demonstrated a dose and time dependent production and release of a PDGF-like growth factor from irradiated BAEC detected by its mitogenic activity on BALB/3T3 cells. The possible relevance of these phenomena to the pathogenesis and repair of irradiation induced vascular damage observed in vivo is discussed