Poso A, von Wright A, Gynther J
Department of Pharmaceutical Chemistry, University of Kuopio, Finland.
Mutat Res. 1995 Nov;332(1-2):63-71. doi: 10.1016/0027-5107(95)00155-2.
Hydrazine compounds are important industrial and laboratory chemicals. Many of them are carcinogenic in animal tests. Although the carcinogenicity is well established, the results of mutagenicity tests performed on alkylhydrazines vary greatly in different studies. In an attempt to clarify the situation we have applied Salmonella typhimurium TA102 tests to hydrazine and its mono- and dimethyl derivatives. These compounds were also tested by an Escherichia coli DNA repair-assay. The results of the repair tests indicate that unsymmetrically alkylated hydrazines can cause DNA-lesions which are lethal in repair-deficient strains. Finally QSAR (Quantitative Structure Activity Relationships) was used to develop a model to describe the genotoxic mechanism of hydrazine compounds, taking advantage of the results of previous mutagenicity studies. Energy of the lowest unoccupied molecular orbital together with octanol-water partition coefficient explains nearly completely the mutagenic activity of alkylated hydrazine compounds included in the analysis. The mutagenic activity of unsubstituted hydrazine is apparently based on different mechanisms.
肼类化合物是重要的工业和实验室化学品。其中许多在动物试验中具有致癌性。尽管致癌性已得到充分证实，但对烷基肼进行的致突变性试验结果在不同研究中差异很大。为了澄清这种情况，我们对肼及其单甲基和二甲基衍生物进行了鼠伤寒沙门氏菌TA102试验。这些化合物还通过大肠杆菌DNA修复试验进行了检测。修复试验结果表明，不对称烷基化肼可导致DNA损伤，这在修复缺陷菌株中是致命的。最后，利用先前致突变性研究的结果，采用定量构效关系（QSAR）建立了一个模型来描述肼类化合物的遗传毒性机制。最低未占据分子轨道的能量与正辛醇-水分配系数几乎完全解释了分析中所包含的烷基化肼化合物的致突变活性。未取代肼的致突变活性显然基于不同的机制。
