WR-1065 and radioprotection of vascular endothelial cells. I. Cell proliferation, DNA synthesis and damage

Journal Article · Wed Jan 31 23:00:00 EST 1996 · Radiation Research

DOI:https://doi.org/10.2307/3579176· OSTI ID:387319

Rubin, D B; Drab, E A; Kang, H J; Baumann, F E; Blazek, E R ^[1]

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1. Rush Univ. Medical College, Chicago, IL (United States)

Normal tissue toxicity limits radiation therapy and could depend on the extent of damage to the vascular endothelium. Aminothiols such as WR-1065 [N-(2-mercaptoethyl)-1,3-diaminopropane] provide radioprotection for normal tissues, but little is known about how the aminothiols specifically affect the endothelium. Bovine aortic endothelial cells in culture were exposed to WR-1065 for 2 h before irradiation ({sup 137}Cs {gamma} rays, 1 Gy/min). Alone, WR-1065 demonstrated an antiproliferative effect that was related to dose (0.5-4 mM) and was evident by lowered counts of adherent cells 48 h after exposure. WR-1065 was clearly radioprotective when assessed by colony formation and incorporation of [{sup 3}H]thymidine. However, when the number of adherent cells was evaluated, radioprotection appeared to be slight and evident only in logarithmically growing cells. WR-1065 at 2 mM suppressed single-strand DNA breaks after 3 Gy by 22% and double-strand breaks after 9 Gy by 47%. Also in the irradiated cells, WR-1065 more than doubled the rate of progression of cells from G{sub 1} to S phase. WR-1065 pretreatment elevated cellular glutathione (GSH) content more than twofold. Although pretreatment with buthionine sulfoximine inhibited the elevation of GSH, the radioprotective impact of WR-1065 on total DNA strand breaks and colony formation was unaffected. These results suggest that WR-1065 may enable tissue recovery from irradiation by promoting the replication of endothelial cells, possibly by mechanisms independent of GSH. 46 refs., 6 figs., 2 tabs.

• Sponsoring Organization: USDOE
• OSTI ID: 387319
• 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
BIOSYNTHESIS
CELL PROLIFERATION
DNA
DNA REPLICATION
ENDOTHELIUM
GAMMA RADIATION
GENETIC RADIATION EFFECTS
GLUTATHIONE
IONIZING RADIATIONS
MUTATIONS
RADIATION DOSES
RADIATION INJURIES
RADIOPROTECTIVE SUBSTANCES
RADIOTHERAPY
STRAND BREAKS