Franko A J
Radiat Res. 1985 Jul;103(1):89-97.
Misonidazole has been shown to bind selectively to hypoxic cells in tissue culture and to cells which are presumed to be chronically hypoxic in EMT6 spheroids and tumors. Thus it has considerable potential as a marker of hypoxic cells in vivo. To further evaluate this potential EMT6/Ed spheroids were used to quantitate misonidazole binding under conditions which resulted in hypoxic fractions between 0 and 1. Hypoxic fractions were quantitated using radiation survival curves. A doubling of the oxygen in the gas phase to 40% was required to fully oxygenate all chronically hypoxic cells. The patterns of binding of 14C-labeled misonidazole determined by autoradiography were consistent with the regions of radiobiological hypoxia as predicted by oxygen diffusion theory. The overall uptake of 3H-labeled misonidazole by spheroids correlated well with the hypoxic fraction, although binding to aerobic cells and necrotic tissue contributed appreciably to the total label in the spheroids. It is concluded that misonidazole is an excellent marker of hypoxia in EMT6/Ed spheroids at the microscopic level, and the total amount bound per spheroid provides a potentially useful measure of the hypoxic fraction.
甲硝唑已被证明在组织培养中能选择性地与缺氧细胞结合，也能与EMT6球体和肿瘤中被认为长期处于缺氧状态的细胞结合。因此，它在体内作为缺氧细胞的标志物具有相当大的潜力。为了进一步评估这种潜力，使用EMT6/Ed球体在导致缺氧分数在0到1之间的条件下对甲硝唑结合进行定量。使用辐射存活曲线对缺氧分数进行定量。需要将气相中的氧气含量加倍至40%才能使所有长期缺氧细胞完全充氧。通过放射自显影确定的14C标记甲硝唑的结合模式与氧扩散理论预测的放射生物学缺氧区域一致。球体对3H标记甲硝唑的总体摄取与缺氧分数密切相关，尽管与有氧细胞和坏死组织的结合对球体中的总标记有相当大的贡献。结论是，甲硝唑在微观水平上是EMT6/Ed球体中缺氧的优秀标志物，每个球体结合的总量为缺氧分数提供了一个潜在有用的测量方法。
