Binding of 14C-misonidazole to hypoxic cells in V79 spheroids.

Binding of 14C-misonidazole to hypoxic cells in V79 spheroids.
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DOI:
10.1038/bjc.1982.110
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发表时间:
1982-05
影响因子:
8.8
通讯作者:
Chapman, J D
Chapman, J D
中科院分区:
医学1区
文献类型:
--
作者:
Franko, A J;Chapman, J D

文献摘要

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代谢诱导结合的14 C-标记的米索硝唑(MISO)缺氧V79细胞在多细胞球体已被定量使用放射自显影。缺氧被证明是结合率的主要决定因素。最大缺氧细胞绑定MISO几倍更快地比坏死材料的中心的球体,并高达50倍更快地比良好的氧合细胞。在坏死中心边缘的慢性缺氧细胞的结合率是20倍,比其他球状体中的类似细胞最大限度地缺氧与N2。这种差异与慢性缺氧细胞的更大的放射敏感性一致,这是它们的中等水平的氧合的结果。结果表明,结合MISO的能力可能具有相当大的潜力,作为肿瘤中缺氧细胞的标志物。然而,一些绑定模式不能解释的最简单的模型O2扩散。可能需要调用影响结合速率的球体内的O2扩散或代谢梯度的更复杂的模型。
The metabolism-induced binding of 14C-labelled misonidazole (MISO) to hypoxic V79 cells in multicell spheroids has been quantitated using autoradiography. Hypoxia was shown to be the major determinant of the rate of binding. Maximally hypoxic cells bound MISO several times more rapidly than necrotic material in the centre of the spheroids, and up to 50 times more rapidly than well oxygenated cells. The rate of binding to chronically hypoxic cells at the edge of the necrotic centre was 20 times less than to similar cells in other spheroids made maximally hypoxic with N2. This difference is consistent with the greater radio-sensitivity of the chronically hypoxic cells, which is a consequence of their intermediate level of oxygenation. The results indicated that the ability to bind MISO might have considerable potential as a marker for hypoxic cells in tumours. However, some binding patterns cannot be explained by the simplest model of O2 diffusion. It may be necessary to invoke more complex models of O2 diffusion or metabolic gradients within the spheroid which affect the rate of binding.