Abstract

Purpose

Our previous study indicated that sodium orthovanadate (vanadate), a strong inhibitor of p53, effectively suppressed the lethality from the hematopoietic (HP) and gastrointestinal (GI) syndromes after 12 Gy total-body irradiation (TBI) in mice. This conclusion, however, was inconsistent with the fact that p53 plays a radioprotective role in the intestinal epithelium. The death after TBI of around 12 Gy was attributed to a combined effect of HP and GI syndromes. To verify the effect from prophylactic administration of p53 inhibitor on protection of HP and GI syndromes, in this study, the radioprotective effects from vanadate were investigated in TBI and lower half-body irradiation (partial-body irradiation: PBI) mouse models.

Methods

Female ICR mice were given a single injection of vanadate or vehicle, followed by a lethal dose of TBI or PBI. Radioprotective effects of vanadate against the irradiations were evaluated by analyzing survival rate, body weight, hematopoietic parameters, and histological changes in the bone marrow and intestinal epithelium.

Results

TBI-induced HP syndrome was effectively suppressed by vanadate treatment. After TBI, the vanadate-treated mice retained better bone marrow cellularity and showed markedly higher survival rate compared to the vehicle-treated animals. In contrast, vanadate did not relieve loss of intestinal crypts and failed to rescue mice from GI death after PBI.

Conclusion

Vanadate is a p53 inhibitor that has been shown to be beneficial as a radiation protective agent against HP but was not effective in protecting against acute GI radiation injury.

中文翻译：

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原钒酸钠作为小鼠全身照射和局部照射条件下放射防护剂的评价

 抽象的

 目的

我们之前的研究表明，原钒酸钠（钒酸盐）是p53的强抑制剂，可有效抑制小鼠12 Gy全身照射（TBI）后造血（HP）和胃肠道（GI）综合征的致死率。然而，这一结论与 p53 在肠上皮细胞中发挥辐射防护作用的事实不一致。 TBI 后约 12 Gy 的死亡归因于 HP 和 GI 综合征的综合影响。为了验证预防性施用 p53 抑制剂对 HP 和 GI 综合征的保护作用，在本研究中，在 TBI 和下半身照射（partial-body Radiation：PBI）小鼠模型中研究了钒酸盐的放射防护作用。

 方法

雌性 ICR 小鼠单次注射钒酸盐或载体，然后注射致死剂量的 TBI 或 PBI。通过分析存活率、体重、造血参数以及骨髓和肠上皮的组织学变化来评估钒酸盐对辐射的辐射防护作用。

 结果

钒酸盐治疗可有效抑制 TBI 诱发的 HP 综合征。 TBI 后，与载体治疗的小鼠相比，钒酸盐治疗的小鼠保留了更好的骨髓细胞结构，并且显示出显着更高的存活率。相比之下，钒酸盐不能缓解肠隐窝的损失，也不能挽救 PBI 后胃肠道死亡的小鼠。

 结论

钒酸盐是一种 p53 抑制剂，已被证明可作为抗 HP 的辐射防护剂，但不能有效预防急性胃肠道辐射损伤。