WR-1065 and radioprotection of vascular endothelial cells. II. Morphology

Journal Article · Thu Feb 01 04:00:00 EST 1996 · Radiation Research

DOI:https://doi.org/10.2307/3579177· OSTI ID:387320

Mooteri, S N; Podolski, J L; Drab, E A; Saclarides, T J ^[1]

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1. Rush Medical College, Chicago, IL (United States); and others

Although the aminothiol WR-1065 protects normal tissues, its direct effect on the damage and restoration of the vascular endothelium is not clear. In endothelial cells, WR-1065 attenuates both the DNA damage and the G{sub 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 morphology and migration, portions of bovine aortic endothelial cell cultures were denuded with a pipette tip and irradiated ({sup 137}Cs {gamma} 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}{sub 5}{Beta}{sub 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. Compared to controls after 24 h, the irradiated cells had migrated 15% farther (P < 0.01), and at the leading edge covered twice the surface area (P < 0.0001). The addition of 2 mM WR-1065 for 2 h before 5 Gy inhibited the increased expression of {alpha}{sub 5}{Beta}{sub 1}, promoted retention of stress fibers and prevented the enhanced cell migration and spreading. These results indicate that WR-1065 prevents radiation-induced morphological responses. This effect appears to be mediated by an impact on both adhesion molecule expression and cytoskeletal reorganization. 61 refs., 6 figs.

• Sponsoring Organization: USDOE
• OSTI ID: 387320
• Journal Information: Radiation Research, Journal Name: Radiation Research Journal Issue: 2 Vol. 145; ISSN RAREAE; ISSN 0033-7587
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
56 BIOLOGY AND MEDICINE
APPLIED STUDIES
ANIMAL CELLS
BIOLOGICAL RADIATION EFFECTS
CELL CYCLE
CELL DIVISION
DNA
ELECTROPHORESIS
ENDOTHELIUM
GENETIC RADIATION EFFECTS
IONIZING RADIATIONS
MIGRATION LENGTH
MORPHOLOGY
MUTATIONS
RADIATION DOSES
RADIOPROTECTIVE SUBSTANCES