Direct evidence for a bystander effect of ionizing radiation in primary human fibroblasts.
Direct evidence for a bystander effect of ionizing radiation in primary human fibroblasts.
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DOI：
10.1054/bjoc.2000.1665
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发表时间：
2001-03-02
影响因子：
8.8
通讯作者：
Michael BD
中科院分区：
文献类型：
--
作者：
Belyakov OV;Malcolmson AM;Folkard M;Prise KM;Michael BD
旁观者反应是目前开发癌症基因治疗方法的一些努力的基础。同样，它们可能在用靶向放射性同位素治疗肿瘤的策略中发挥作用。在这项研究中，我们显示了直接的证据，在原代人成纤维细胞辐射诱导的旁观者反应的生产。我们利用一种新的方法，使用带电粒子微束，它允许在一个群体中的单个细胞被选择和计数的带电粒子为目标。用1 - 15个氦离子（有效地，α粒子）靶向600-800个细胞群体中的单个原代人成纤维细胞。带电粒子通过原子核中心，精度为± 2 μm，探测和计数效率大于99%。当在3天后评分时，即使仅靶向单个细胞，通常在约5000个细胞的存活群体中观察到另外80-100个受损细胞。受损细胞的产量与递送到靶细胞的带电粒子的数量无关。无论在培养皿内靶向1个或4个细胞，均观察到群体中存在的背景损伤水平增加2-3倍的类似结果。此外，当培养皿的一个象限内的200个细胞暴露于辐射时，培养皿的未暴露象限中的损伤水平增加2-3倍。该效应与培养基中血清的存在无关，并且仅在靶向细胞时观察到，而在仅暴露培养基时未观察到，证实涉及细胞介导的应答。© 2001年癌症研究运动http://www.bjcancer.com
Bystander responses underlie some of the current efforts to develop gene therapy approaches for cancer treatment. Similarly, they may have a role in strategies to treat tumours with targeted radioisotopes. In this study we show direct evidence for the production of a radiation-induced bystander response in primary human fibroblasts. We utilize a novel approach of using a charged-particle microbeam, which allows individual cells within a population to be selected and targeted with counted charged particles. Individual primary human fibroblasts within a population of 600–800 cells were targeted with between 1 and 15 helium ions (effectively, α-particles). The charged particles were delivered through the centre of the nucleus with an accuracy of ± 2 μm and a detection and counting efficiency of greater than 99%. When scored 3 days later, even though only a single cell had been targeted, typically an additional 80–100 damaged cells were observed in the surviving population of about 5000 cells. The yield of damaged cells was independent of the number of charged particles delivered to the targeted cell. Similar results of a 2–3-fold increase in the background level of damage present in the population were observed whether 1 or 4 cells were targeted within the dish. Also, when 200 cells within one quadrant of the dish were exposed to radiation, there was a 2–3-fold increase in the damage level in an unexposed quadrant of the dish. This effect was independent of the presence of serum in the culture medium and was only observed when a cell was targeted, but not when only the medium was exposed, confirming that a cell-mediated response is involved. © 2001 Cancer Research Campaign http://www.bjcancer.com
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DOI：
10.1073/pnas.95.10.5730
发表时间：
1998-05-12
影响因子：
11.1
作者：
Lorimore, SA;Kadhim, MA;Wright, EG
通讯作者：
Wright, EG
影响因子：
2.6
作者：
Prise, KM;Belyakov, OV;Michael, BD
通讯作者：
Michael, BD
DOI：
10.1073/pnas.030420797
发表时间：
2000-02-29
影响因子：
11.1
作者：
Zhou, HN;Randers-Pehrson, G;Hei, TK
通讯作者：
Hei, TK
影响因子：
3.4
作者：
Narayanan, PK;LaRue, KEA;Lehnert, BE
通讯作者：
Lehnert, BE
影响因子：
2.6
作者：
Folkard, M;Vojnovic, B;Michael, BD
通讯作者：
Michael, BD