Induction of lethal bystander effects in human breast cancer cell cultures by DNA-incorporated Iodine-125 depends on phenotype.
Induction of lethal bystander effects in human breast cancer cell cultures by DNA-incorporated Iodine-125 depends on phenotype.
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DNA 掺入的 Iodine-125 在人类乳腺癌细胞培养物中诱导致命的旁观者效应取决于表型。
DOI：
10.3109/09553002.2012.683511
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发表时间：
2012-12
影响因子：
2.6
通讯作者：
Howell RW
中科院分区：
文献类型：
--
作者：
Akudugu JM;Azzam EI;Howell RW
本研究采用三维细胞培养模型，研究了125I标记的5-碘-2‘-脱氧尿苷(125IdU)对人乳腺癌细胞(MCF-7、MDA-MB-231)的致死性旁观者效应。这些乳腺癌细胞系分别以雌激素依赖和独立的方式在裸鼠体内形成转移性异种移植瘤。在本研究中，这些细胞被培养在松散排列的三维结构中，放置在Cytomatrix™碳支架中。用125IdU脉冲标记培养3h，选择性照射一小部分细胞，同时用0.04 mM 5-乙炔基-2‘-脱氧尿苷(EDU)共脉冲标记，用Click-it®EDU和流式细胞仪鉴定标记细胞。然后洗涤培养48h，然后收获细胞，连续稀释，接种以形成克隆。流式细胞仪检测标记125IdU/EDU的细胞百分率。使用附加等分线来确定每个标记细胞的平均125I活度。MCF-7和MDA-MB-231细胞的标记细胞百分率分别约为15%和10%。这创造了辐射条件，其中对未标记细胞的交叉剂量相对于对标记细胞的自身剂量较小。与EDU处理的对照组相比，测量存活分数。生存曲线显示在MCF-7细胞中存在显著的旁观者效应，而在MDA-MB-231细胞中未观察到明显的旁观者效应。这些研究证明了125IdU在人类乳腺癌细胞中诱导致命性旁观者效应的能力，并表明这种反应取决于表型。
This study uses a three-dimensional cell culture model to investigate lethal bystander effects in human breast cancer cell cultures (MCF-7, MDA-MB-231) treated with 125I-labeled 5-iodo-2′-deoxyuridine (125IdU). These breast cancer cell lines respectively form metastatic xenografts in nude mice in an estrogen-dependent and independent manner. In the present study, these cells were cultured in loosely-packed three-dimensional architecture in a Cytomatrix™ carbon scaffold. Cultures were pulse-labeled for 3 h with 125IdU to selectively irradiate a minor fraction of cells, and simultaneously co-pulse-labeled with 0.04 mM 5-ethynyl-2′-deoxyuridine (EdU) to identify the radiolabeled cells using Click-iT® EdU and flow cytometry. The cultures were then washed and incubated for 48 h. The cells were then harvested, serially diluted, and seeded for colony formation. Aliquots of cells were subjected to flow cytometry to determine the percentage of cells labeled with 125IdU/EdU. Additional aliquots were used to determine the mean 125I activity per labeled cell. The percentage of labeled cells was about 15% and 10% for MCF-7 and MDA-MB-231 cells, respectively. This created irradiation conditions wherein the cross-dose to unlabeled cells was small relative to the self-dose to labeled cells. The surviving fraction relative to EdU-treated controls was measured. Survival curves indicated significant lethal bystander effect in MCF-7 cells, however, no significant lethal bystander effect was observed in MDA-MB-231 cells. These studies demonstrate the capacity of 125IdU to induce lethal bystander effects in human breast cancer cells and suggest that the response depends on phenotype.
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影响因子：
3.3
作者：
Boyd, Marie;Sorensen, Annette;Mairs, Robert J.
通讯作者：
Mairs, Robert J.
影响因子：
3.4
作者：
BROOKS, AL;RETHERFORD, JC;MCCLELLAN, RO
通讯作者：
MCCLELLAN, RO
影响因子：
2
作者：
Autsavapromporn N;De Toledo SM;Buonanno M;Jay-Gerin JP;Harris AL;Azzam EI
通讯作者：
Azzam EI
影响因子：
3.4
作者：
HOWELL, RW;RAO, DV;SASTRY, KSR
通讯作者：
SASTRY, KSR
影响因子：
3.4
作者：
Chang, CC;Sun, W;Trosko, JE
通讯作者：
Trosko, JE