The dynamics of the endothelial cell population was investigated in the rat brain after local irradiation with different doses of X rays. A fluorescent-histochemical technique was used for the visualization of the cells. A decrease in endothelial cell number was observed within 1 day of irradiation with doses of 5-200 Gy. At this time the endothelial cell number had decreased by up to 15% compared with the pre-treatment values. This early dose-independent loss in cell number was maintained for up to 1 month after irradiation. This was then followed by a slow dose-independent decrease in cell density up to 6 months after exposure. Subsequently the depletion of the endothelial cell population exposed to 40 and 60 Gy continued. After a dose of 25 Gy an abortive recovery of cell numbers occurred followed by an abrupt depletion of the endothelial cell population. The possible mechanisms of such changes are discussed.

The present study demonstrates that DNA fragmentation, nuclear pycnosis and trypan blue staining of irradiated thymocytes is prevented by inhibition of the lipoxygenase pathway of arachidonic acid metabolism and is not affected by cyclooxygenase inhibition. Exposed to irradiation [3H]arachidonic acid-labeled thymocytes release radioactive products to the external medium. The process is blocked by the lipoxygenase inhibitor, nordihydroguaiaretic acid. Thus, it can be concluded that irradiation activates arachidonic acid metabolism and that lipoxygenase metabolites play an important role in thymocyte apoptosis.

In vitro permittivity measurements of excised human liver, spleen, kidney and cardiac muscle at frequencies from 10 kHz to 100 MHz are described. An end-of-the-line capacitive sensor and a computer-controlled network analyser HP 3577 were employed. The results were compared with human data reported by other investigators as well as with the animal (cat) data obtained earlier in this laboratory. It was found that the conductivity of most of the human tissues tested was significantly higher than that of the animal tissues for the test frequencies. The dielectric constants for human kidney and spleen are higher than the corresponding animal (cat) tissues at frequencies from 10 kHz to approximately 1 MHz and at around 100 MHz. However, the values for liver do not differ significantly between the two species in the same frequency range.

The effect of inhibitors and activators of protein kinase C and phospholipase A, on radiation-induced apoptosis of rat and mouse thymocytes has been studied. It is shown that the apoptosis is prevented by the protein kinase C inhibitor I-(5-isoquinolinylsulfonyl)-2-methylpiperasine dihydrochloride and is potentiated by protein kinase C activator phorbol 12-myristate 13-acetate, calcium ionophore A23187 and concanavalin A. The protein kinase C activators initiate apoptosis in mouse but not in rat thymocytes. The inhibitor of phospholipase Az prevents apoptosis induced by all the factors. The results obtained indicate that both protein kinase C and phospholipase A, are involved in the thymocyte apoptosis.

The effect of the interaction of different types of cells on the interphase death and pycnosis of thymocytes irradiated in vitro was studied. When removed from the thymus suspension of cells with natural killer activity, medullary thymocytes and macrophages did not change the radiation-induced death of cortical thymocytes. On the other hand, postirradiation incubation of cortical thymocytes together with unirradiated thymocytes or with cells of certain other cell lines diminished thymocyte death. Mixing the cell suspensions and changing the incubation medium decreased thymocyte death. All of these results indicate that these cells produce soluble mediators that are toxic to the cells that secrete them. The possible nature of these autotoxic mediators has been studied using inhibitors of arachidonic acid metabolism. Inhibitors of phospholipase A2 or lipoxygenase reduced interphase death markedly, while an inhibitor of cyclooxygenase did not. These data suggest that some lipoxygenase products may serve as autotoxic mediators in the interphase death of thymocytes.