The effect of dexamethasone on the cytotoxic and enzymatic response of cultured endothelial cells to radiation.
Experiments were conducted to determine (1) whether glucocorticoids directly protected endothelial cells (EC) from radiation and (2) if angiotensin converting enzyme (ACE) activity, known to be increased by glucocorticoid, played a role in the EC response to radiation. Confluent monolayers of EC cultured from bovine aorta EC were treated with dexamethasone (10(-6) M); after irradiation (5.0 Gy, 60Co gamma), ACE and lactate dehydrogenase (LDH) activities, DNA and protein contents, and nuclei number were measured. Twenty-four hours after 5 Gy, there was increased cell loss (-40%, P less than 0.001), greater LDH release (greater than 100%, P less than 0.001), more LDH activity per cell (+40%, P less than 0.001), and unchanged ACE activity compared to sham-irradiated control EC. However, 48 hr after 5 Gy, ACE activity per cell was decreased (-24%, P less than 0.005). A 48-hr exposure to dexamethasone alone was accompanied by a slight cell loss (-10%, P less than 0.001) and increased cellular ACE activity (+40-140%, P less than 0.001), but a 24-hr dexamethasone exposure was not cytotoxic and did not change ACE activity. Dexamethasone exposure for 48 hr before and after irradiation did not attenuate cell loss or LDH release. However, combined dexamethasone treatment and radiation increased cellular ACE activity at a time when neither agent alone had an effect (24-hr dexamethasone exposure before 5 Gy and assayed 24 hr after 5 Gy). This interaction between radiation and dexamethasone treatment suggests that the glucocorticoid modifies the cell's response to injury. Although this interaction does not ameliorate radiation cytotoxicity, maintenance of ACE levels in injured vessels by hormones may have physiological significance in the hemodynamics of irradiated tissues.
Lam
T T
TT
Rubin
D
D
Drab
E A
EA
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D003037:Cobalt Radioisotopes; D003907:Dexamethasone / Q000494:pharmacology*; D005720:Gamma Rays; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000502:physiology; D011837:Radiation-Protective Agents / Q000494:pharmacology*
D003037:Cobalt Radioisotopes; D011837:Radiation-Protective Agents; D003907:Dexamethasone; D007770:L-Lactate Dehydrogenase; D007703:Peptidyl-Dipeptidase A