Bystander-induced differentiation: A major response to targeted irradiation of a urothelial explant model

Bystander-induced differentiation: A major response to targeted irradiation of a urothelial explant model
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DOI:
10.1016/j.mrfmmm.2005.08.012
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发表时间:
2006-05-11
影响因子:
2.3
通讯作者:
Michael, Barry D.
Michael, Barry D.
中科院分区:
医学4区
文献类型:
--
作者:
Belyakov, Oleg V.;Folkard, Melvyn;Michael, Barry D.

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开发了一种使用猪组织切片的输尿管原代外植体技术,用于研究在存在分裂和分化细胞的体内类似条件下的旁观者效应。使用格雷癌症研究所带电粒子微束在单个位置(精度为 2 μm)用 10 个 He-3(2+) 粒子(5 MeV;LET 70 keV/μm)对输尿管组织碎片进行靶向照射。照射后,将输尿管组织切片孵育7天,以形成外植体生长。使用 Uroplakin III 抗体评估分化,Uroplakin III 是终末尿路上皮分化的特异性标志物。尽管只针对组织切片的单个区域,但在外植体生长中发现了数千个额外的细胞经历旁观者诱导的分化。这导致分化细胞比例从 63.5 +/- 5.4% 总体增加到 76.6 +/- 5.6%。这些变化远大于在该模型中观察到的诱导损坏的变化。对这些结果的一种解释是,在组织环境中,分化是对靶向照射的更重要的反应,并且可能是一种保护机制。 (c) 2005 Elsevier B.V. 保留所有权利。
A ureter primary explant technique, using porcine tissue sections was developed to study bystander effects under in vivo like conditions where dividing and differentiated cells are present. Targeted irradiations of ureter tissue fragments were performed with the Gray Cancer Institute charged particle microbeam at a single location (2 mu m precision) with 10 He-3(2+) particles (5 MeV; LET 70 keV/mu m). After irradiation the ureter tissue section was incubated for 7 days allowing explant outgrowth to be formed. Differentiation was estimated using antibodies to Uroplakin III, a specific marker of terminal urothelial differentiation. Even although only a single region of the tissue section was targeted, thousands of additional cells were found to undergo bystander-induced differentiation in the explant outgrowth. This resulted in an overall increase in the fraction of differentiated cells from 63.5 +/- 5.4% to 76.6 +/- 5.6%. These changes are much greater than that observed for the induction of damage in this model. One interpretation of these results is that in the tissue environment, differentiation is a much more significant response to targeted irradiation and potentially a protective mechanism. (c) 2005 Elsevier B.V. All rights reserved.