Koch C J, Howell R L
Int J Radiat Oncol Biol Phys. 1982 Mar-Apr;8(3-4):693-6. doi: 10.1016/0360-3016(82)90714-3.
A detailed investigation was undertaken of reported modifiers of the toxicity towards hypoxic cells of misonidazole. The modifiers tested were medium type, cell type, cell density, concentration of misonidazole, addition of serum, addition of sulfhydryl, addition of oxygen and pH. The latter 5 modifiers were found to be most important and were studied in many of the possible combinations. Serum has its greatest protective effect at low concentration (e.g. 0.5 mM) of misonidazole. In the absence of serum, the (log10) survival curve for misonidazole toxicity can be described mathematically as a function of time by a shoulder (DQ) inversely related to misonidazole concentration, and a slope (1/D0) related directly to log10 misonidazole concentration. Sulfhydryl's (cysteamine) protective effect dominates at high concentrations of misonidazole. The protective action of SH can change to potentiative in the absence of serum or at high pH. Addition of oxygen results in overall protection but no relative changes in the effect of the other modifiers. Drugs like ascorbate and disulfide may only potentiate toxicity to the level found in the absence of serum.
对已报道的米索硝唑对缺氧细胞毒性的修饰剂进行了详细研究。所测试的修饰剂包括培养基类型、细胞类型、细胞密度、米索硝唑浓度、血清添加、巯基添加、氧气添加和pH值。发现后5种修饰剂最为重要，并对许多可能的组合进行了研究。血清在低浓度（如0.5 mM）的米索硝唑时具有最大的保护作用。在无血清的情况下，米索硝唑毒性的（log10）存活曲线在数学上可描述为时间的函数，其肩部（DQ）与米索硝唑浓度呈反比，斜率（1/D0）与log10米索硝唑浓度直接相关。巯基（半胱胺）的保护作用在高浓度米索硝唑时占主导。在无血清或高pH值条件下，SH的保护作用可转变为增效作用。添加氧气可带来总体保护，但其他修饰剂的效果无相对变化。像抗坏血酸盐和二硫化物这样的药物可能只会将毒性增强到无血清时的水平。
