Evidence for pronounced bystander effects caused by nonuniform distributions of radioactivity using a novel three-dimensional tissue culture model
Evidence for pronounced bystander effects caused by nonuniform distributions of radioactivity using a novel three-dimensional tissue culture model
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DOI：
10.2307/3580054
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发表时间：
1999-07-01
影响因子：
3.4
通讯作者：
Howell, RW
中科院分区：
文献类型：
--
作者：
Bishayee, A;Rao, DV;Howell, RW
开发了一种新的体外多细胞簇模型，用于评估放射性不均匀分布对哺乳动物细胞生物反应的影响，以及与传统辐射效应相比旁观者效应的相对重要性。中国仓鼠V79细胞用氚化胸苷([H-3]dThd)标记，与未标记的V79细胞混合，轻轻离心形成直径约1.6mm的多细胞簇。 H-3 β粒子的短射程有效地仅允许标记细胞的自照射，而不允许未标记细胞的交叉照射。通过在组装簇之前改变与未标记细胞混合的标记细胞的数量来精确控制标记细胞的百分比。在不存在或存在100μM林丹（一种已知抑制间隙连接形成的化学物质）的情况下组装簇。将细胞簇在 10.5°C 下维持 72 小时后，将细胞分散并铺板以形成集落。在 100% 标记的情况下，簇中细胞的存活率以指数方式 (SF = e(-A/1.8)) 取决于簇活性 A（以 kBq 为单位），林丹对响应没有影响。 ii 在没有林丹的情况下，50% 标记获得双分量指数响应 (SF = 0.33 e(-A/0.81) + 0.67 e(-A/11.8))，林丹对响应有显着影响 (SF = 0.33 e(-A/1.6) + 0.67 e(-A/41.6) ）。这些数据表明，当H-3位于细胞核中并且在细胞间分布不均匀时，旁观者效应在V79细胞的生物反应中发挥重要作用。相比之下，当 H-3 位于细胞核中并均匀分布在细胞之间时，旁观者效应无法检测到高于传统辐射效应（即直接+间接）。这些结果表明，这种多细胞簇模型非常适合研究放射性不均匀分布的影响，包括旁观者效应和“热粒子”效应。此外，这些结果表明旁观者效应可能在预测医疗诊断和治疗中使用的放射性药物的生物效应中发挥重要作用。 (C) 1999 年，辐射研究学会。
A new in vitro multicellular cluster model has been developed to assess the impact of nonuniform distributions of radioactivity on the biological response of mammalian cells, and the relative importance of bystander effects compared to conventional radiation effects. Chinese hamster V79 cells are labeled with tritiated thymidine ([H-3]dThd), mixed with unlabeled V79 cells, and centrifuged gently to form multicellular clusters about 1.6 mm in diameter. The short range of the H-3 beta particles effectively allows only self-irradiation of labeled cells and no cross-irradiation of unlabeled cells,The percentage of labeled cells is controlled precisely by varying the number of labeled cells mixed with unlabeled cells prior to assembling the cluster, The clusters are assembled in the absence or presence of 100 mu M lindane, a chemical that is known to inhibit formation of gap junctions. After the clusters are maintained at 10.5 degrees C for 72 h, the cells are dispersed and plated for colony formation. In the case of 100% labeling, the survival of cells in the cluster depends exponentially (SF = e(-A/1.8)) on the cluster activity A (in kBq), and lindane has no effect on the response. ii two-component exponential response is obtained for 50% labeling in the absence of lindane (SF = 0.33 e(-A/0.81) + 0.67 e(-A/11.8)), and lindane has a marked effect on the response (SF = 0.33 e(-A/1.6) + 0.67 e(-A/41.6) ). These data suggest that bystander effects play an important role in the biological response of V79 cells when the H-3 is localized in the cell nucleus and distributed nonuniformly among the cells. In contrast, bystander effects cannot be detected above traditional radiation effects (i.e. direct + indirect) when the H-3 is localized in the cell nucleus and distributed uniformly among the cells. These results indicate that this multicellular cluster model is well suited for studying the effects of nonuniform distributions of radioactivity, including bystander and "hot-particle" effects. Furthermore, these results suggest that by-stander effects may play an important role in the prediction of the biological effects of radiopharmaceuticals used in medical diagnosis and treatment. (C) 1999 by Radiation Research Society.