LOW-DOSE RADIATION-INDUCED ENDOTHELIAL-CELL RETRACTION

We characterized in vitro the effects of 7-radiation (12.5-100 cGy) on pulmonary microvascular endothelial cell (PMEC) morphology and F-acti n organization. Cellular retraction was documented by phase-contrast m icroscopy and the organization of actin microfilaments was determined by immunofluorescence. Characterization included radiation dose effect s, their temporal duration and reversibility of the effects. A dose-de pendent relationship between the level of exposure (12.5-100 cGy) and the rate and extent of endothelial retraction was observed. Moreover, analysis of radiation-induced depolymerization of F-actin microfilamen t stress fibres correlated positively with the changes in PMEC morphol ogy. The depolymerization of the stress fibre bundles was dependent on radiation dose and time. Cells recovered from exposure to reform cont act inhibited monolayers greater-than-or-equal-to 24h post-irradiation . Concomitantly, the depolymerized microfilaments reorganized to their preirradiated state as microfilament stress fibres arrayed parallel t o the boundaries of adjacent contact-inhibited cells. The data present ed here are representative of a series of studies designed to characte rize low-dose radiation effects on pulmonary microvascular endothelium . Our data suggest that post-irradiation lung injuries (e.g. oedema) m ay be induced with only a single fraction of therapeutic radiation, an d thus microscopic oedema may initiate prior to the lethal effects of radiation on the microvascular endothelium, and much earlier than woul d be suggested by the time course for clinically-detectable oedema.