WR-1065 AND RADIOPROTECTION OF VASCULAR ENDOTHELIAL-CELLS .2. MORPHOLOGY

Although the aminothiol WR-1065 protects normal tissues, its direct ef fect on the damage and restoration of the vascular endothelium is not clear. In endothelial cells, WR-1065 attenuates both the DNA damage an d the G(1)-phase arrest induced by radiation. After the destruction of nearby endothelial cells, the survivors rearrange their cytoskeleton, migrate and replicate. To determine the effect of radiation on morpho logy and migration, portions of bovine aortic endothelial cell culture s were denuded with a pipette tip and irradiated (Cs-137 Y rays). The following observations were noted after 5 Gy: within 10 min, there was increased formation of protein-mixed disulfides including actin-mixed disulfide; after 30 min, alpha(5) beta(1), the integrin receptor for fibronectin, was up-regulated on the apical membrane surface. Within 5 h, actin-containing stress fibers reorganized, although there was no change in the total filamentous (F-)actin content within the cells. Co mpared to controls after 24 h, the irradiated cells had migrated 15% f arther (P < 0.01), and at the leading edge covered twice the surface a rea (P < 0.0001). The addition of 2 mM WR-1065 for 2 h before 5 Gy inh ibited the increased expression of alpha(5) beta(1), promoted retentio n of stress fibers and prevented the enhanced cell migration and sprea ding. These results indicate that WR-1065 prevents radiation-induced m orphological responses. This effect appears to be mediated by an impac t on both adhesion molecule expression and cytoskeletal reorganization . (C) 1996 by Radiation Research Society.