WR-1065 and radioprotection of vascular endothelial cells .1. Cell proliferation, DNA synthesis and damage
WR-1065 and radioprotection of vascular endothelial cells .1. Cell proliferation, DNA synthesis and damage
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DOI：
10.2307/3579176
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发表时间：
1996-02-01
影响因子：
3.4
通讯作者：
Blazek, ER
中科院分区：
文献类型：
--
作者：
Rubin, DB;Drab, EA;Blazek, ER
正常组织毒性限制了放射治疗，并且可能取决于对血管内皮的损伤程度。氨基硫醇如WR-1065 [N-（2-巯基乙基）-1，3-二氨基丙烷]可为正常组织提供辐射保护，但对氨基硫醇如何特异性影响内皮知之甚少。将培养的牛主动脉内皮细胞暴露于WR-1065 2小时，然后照射（Cs-137 γ射线，1戈伊/min）。WR-1065单独显示出与剂量（0.5-4 mM）相关的抗增殖作用，并且通过暴露后48 h贴壁细胞计数降低而明显。当通过集落形成和[H-3]胸苷掺入评估时，WR-1065具有明显的辐射保护作用。然而，当贴壁细胞的数量进行了评价，辐射保护似乎是轻微的，明显的，只有在cummically生长的细胞。2 mM WR-1065在3戈伊后抑制单链DNA断裂22%，在9戈伊后抑制双链断裂47%。同样在辐照的细胞中，WR-1065使细胞从G（1）期进展到S期的速率增加了一倍以上。WR-1065预处理使细胞谷胱甘肽（GSH）含量增加两倍以上。虽然预处理丁噻呋亚砜亚胺抑制GSH的升高，WR-1065对总DNA链断裂和集落形成的辐射保护作用不受影响。这些结果表明，WR-1065可能通过促进内皮细胞的复制，可能通过独立于GSH的机制，使组织从辐射中恢复。(C)1996年，辐射研究学会
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 (Cs-137 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 [H-3]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(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. (C) 1996 by Radiation Research Society