Edwards D I, Knight R C, Zahoor A
Int J Radiat Oncol Biol Phys. 1986 Jul;12(7):1207-9. doi: 10.1016/0360-3016(86)90259-2.
The effect of pH on E. coli DNA damage measured viscometrically and induced by electrolytically reduced metronidazole and misonidazole has been studied, together with the effect on the statistical average number of electrons required for reduction, measured by high-resolution coulometry, and nitrite production measured colorimetrically. In general, nitroimidazole-induced DNA damage is greatest at acid pH and decreased at alkaline pH, but whereas metronidazole exhibits a linear relationship between DNA damage and increased pH, misonidazole shows a plateau between pH 6 and 8. The electron requirements for complete reduction (n) vary with pH. For misonidazole n increases with an increase in pH both in the absence and presence of DNA with a shallow plateau between pH 6 and 8. In contrast, for metronidazole, n decreases with increased pH and exhibits breakpoints between pH 6 and 8. Nitrite (NO2-) production is linear with increased pH for misonidazole but for metronidazole (NO2-) production shows a sudden increase at 7.5 yielding ca. 35% on a molar basis. The results may reflect differences in the relative stability and reactivity of the nitro radical anion.
研究了pH对通过粘度测定法测量的、由电解还原甲硝唑和米索硝唑诱导的大肠杆菌DNA损伤的影响，以及对通过高分辨率库仑法测量的还原所需统计平均电子数的影响，还有通过比色法测量的亚硝酸盐生成的影响。一般来说，硝基咪唑诱导的DNA损伤在酸性pH下最大，在碱性pH下降低，但甲硝唑在DNA损伤与pH升高之间呈现线性关系，而米索硝唑在pH 6至8之间呈现平稳状态。完全还原所需的电子数（n）随pH而变化。对于米索硝唑，无论有无DNA，n都随pH升高而增加，在pH 6至8之间有一个平缓的平稳状态。相比之下，对于甲硝唑，n随pH升高而降低，在pH 6至8之间出现转折点。米索硝唑的亚硝酸盐（NO2-）生成随pH升高呈线性关系，但甲硝唑的（NO2-）生成在pH 7.5时突然增加，以摩尔计约为35%。这些结果可能反映了硝基自由基阴离子相对稳定性和反应性的差异。
