RADIATION-INDUCED APOPTOSIS IN MICROVASCULAR ENDOTHELIAL-CELLS

The response of the microvasculature to ionizing radiation is thought to be an important factor in the overall response of both normal tissu es and tumours. It has recently been reported that basic fibroblast gr owth factor (bFGF), a potent mitogen for endothelial cells, protects l arge vessel endothelial cells from radiation-induced apoptosis in vitr o. Microvessel cells are phenotypically distinct from large vessel cel ls. We studied the apoptotic response of confluent monolayers of capil lary endothelial cells (ECs) to ionizing radiation and bFGF. Apoptosis was assessed by identifying changes in nuclear morphology, recording cell detachment rates and by detecting internucleosomal DNA fragmentat ion. Withdrawal of bFGF alone induces apoptosis in these monolayers. T he magnitude of this apoptotic response depends upon the duration of b FGF withdrawal. Irradiation (2-10 Gy) induces apoptosis in a dose-depe ndent manner. Radiation-induced apoptosis occurs in a discrete wave 6- 10 h after irradiation, and radiation-induced apoptosis is enhanced in cultures that are simultaneously deprived of bFGF. For example, 6 h a fter 10 Gy, 44.3% (s.e. 6.3%) of cells in the monolayer simultaneously deprived of bFGF exhibit apoptotic morphology compared with 19.8% (s. e. 3.8%) in the presence of bFGF. These studies show that either bFGF withdrawal or ionizing radiation can induce apoptosis in confluent mon olayers of capillary endothelial cells and that radiation-induced apop tosis can be modified by the presence of bFGF.