Bystander effect produced by radiolabeled tumor cells in vivo
Bystander effect produced by radiolabeled tumor cells in vivo
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DOI：
10.1073/pnas.182209699
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发表时间：
2002-10
影响因子：
11.1
通讯作者：
L. Xue;N. Butler;G. Makrigiorgos;S. Adelstein;A. Kassis
中科院分区：
文献类型：
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作者：
L. Xue;N. Butler;G. Makrigiorgos;S. Adelstein;A. Kassis
旁观者效应，起源于体外照射的细胞，描述了周围细胞的生物学反应，而不是直接被辐射损伤所靶向。为了克服体外组织培养模型的局限性，并确定是否可以在动物中证明由放射性核素体内衰变引发的旁观者效应，5-[125 I]碘-2 ′-脱氧尿苷（125 IUdR）标记的肿瘤细胞对皮下生长的邻近未标记肿瘤细胞产生损伤作用的能力。在裸鼠中进行了研究。用致死剂量的掺入DNA的125 I预标记人结肠癌LS 174 T细胞和LS 174 T细胞的混合物注射小鼠后，对皮下接种的LS 174 T细胞的生长有明显的抑制作用。观察到肿瘤（来源于未标记的细胞）。因为（i）存在于细胞内的125 I是DNA结合的，（ii）衰变的125 I原子发射的电子的约99%具有亚细胞范围（<0.5 μm），和（iii）在生长的肿瘤内未标记的细胞中由放射性标记的细胞沉积的总辐射剂量<10 cGy，我们得出结论，所获得的结果是由125 IUdR标记的细胞内存在和/或释放的因子在体内产生的旁观者效应的结果。这些在体内的研究结果显着影响目前的教条评估的治疗潜力的内部管理的放射性核素。它们还要求重新评价目前用于估计无意中受到内部放射性照射的个人和人口以及正在接受常规诊断核医疗程序的病人所面临风险的方法。
The bystander effect, originating from cells irradiated in vitro, describes the biologic response(s) of surrounding cells not directly targeted by a radiation insult. To overcome the limitations of in vitro tissue culture models and determine whether a bystander effect that is initiated by the in vivo decay of a radionuclide can be demonstrated in an animal, the ability of 5-[125I]iodo-2′-deoxyuridine (125IUdR)-labeled tumor cells to exert a damaging effect on neighboring unlabeled tumor cells growing s.c. in nude mice has been investigated. When mice are injected with a mixture of human colon LS174T adenocarcinoma cells and LS174T cells prelabeled with lethal doses of DNA-incorporated 125I, a distinct inhibitory effect on the growth of s.c. tumor (derived from unlabeled cells) is observed. Because (i) the 125I present within the cells is DNA-bound, (ii) ≈99% of the electrons emitted by the decaying 125I atoms have a subcellular range (<0.5 μm), and (iii) the overall radiation dose deposited by radiolabeled cells in the unlabeled cells within the growing tumor is <10 cGy, we conclude that the results obtained are a consequence of a bystander effect that is generated in vivo by factor(s) present within and/or released from the 125IUdR-labeled cells. These in vivo findings significantly impact the current dogma for assessing the therapeutic potential of internally administered radionuclides. They also call for reevaluation of the approaches currently used for estimating the risks to individuals and populations inadvertently exposed internally to radioactivity as well as to patients undergoing routine diagnostic nuclear medical procedures.