Adams G E, Clarke E D, Gray P, Jacobs R S, Stratford I J, Wardman P, Watts M E, Parrick J, Wallace R G, Smithen C E
Int J Radiat Biol Relat Stud Phys Chem Med. 1979 Feb;35(2):151-60. doi: 10.1080/09553007914550161.
This paper describes measurements of the aerobic cytotoxicity of 42 nitroaromatic and nitroheterocyclic compounds towards Chinese Hamster cells in vitro. The results of acute and chronic exposure were quantified, and the concentration C required to achieve a standard response estimated. Fitting the data to an equation of the form - log C = b0 + b1E, where E is the one-electron reduction potential, explained 47 and 71 per cent of the variance in the acute and chronic aerobic cytotoxicity respectively. The addition of further terms to the equation, quantifying partition properties, was not statistically significant. The coefficient b1 was similar for both acute and chronic exposure; the dependence of both cytotoxicity and radiosensitization efficiency on reduction potential was also similar. A therapeutic ratio derived from these in vitro measurements showed no dependence on redox or partition properties. The insensitivity of cytotoxicity and radiosensitization properties to variations in molecular structure, other than those which influence redox behaviour, offers exceptional flexibility in developing compounds of improved therapeutic ratio.
本文描述了42种硝基芳烃和硝基杂环化合物对中国仓鼠细胞的体外需氧细胞毒性的测量。对急性和慢性暴露的结果进行了量化，并估计了达到标准反应所需的浓度C。将数据拟合到形式为-log C = b0 + b1E的方程中，其中E是单电子还原电位，分别解释了急性和慢性需氧细胞毒性中47%和71%的方差。在方程中添加量化分配特性的其他项在统计学上并不显著。急性和慢性暴露的系数b1相似；细胞毒性和放射增敏效率对还原电位的依赖性也相似。从这些体外测量得出的治疗比率显示出对氧化还原或分配特性的不依赖性。除了影响氧化还原行为的那些因素外，细胞毒性和放射增敏特性对分子结构变化的不敏感性为开发具有更高治疗比率的化合物提供了非凡的灵活性。
