Hooberman B H, Chakraborty P K, Sinsheimer J E
College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
Mutat Res. 1993 Apr;299(2):85-93. doi: 10.1016/0165-1218(93)90085-r.
A quantitative structure-activity relationship approach was used to investigate the mutagenicity of a series of seventeen-monosubstituted propylene oxides in Salmonella typhimurium strains TA100 and TA1535. Mutagenicity in strain TA100, using a liquid suspension assay, was found to correlate with chemical reactivity, as measured by the rates of reaction with two model bionucleophiles, nicotinamide and 4-(4-nitrobenzyl)pyridine. However, since the reactivity of three of the epoxides did not correlate to their Taft sigma * values, as a measure of the electronic effects of substituent groups, neither was their mutagenicity predicted by this substituent constant. The relative mutagenicity for the propylene oxides was different in the liquid suspension assay than that determined by the standard plate incorporation assay and also differed between the two bacterial strains. The assay differences were attributed to epoxide stability. The differences between strains was observed to be due to the response of the error-prone repair system, found only in TA100, to the stronger alkylating agents.
采用定量构效关系方法研究了一系列1,2-单取代环氧丙烷在鼠伤寒沙门氏菌TA100和TA1535菌株中的致突变性。通过液体悬浮试验发现，TA100菌株中的致突变性与化学反应性相关，化学反应性通过与两种模型生物亲核试剂烟酰胺和4-(4-硝基苄基)吡啶的反应速率来衡量。然而，由于三种环氧化物的反应性与其Taft σ*值（作为取代基电子效应的一种度量）不相关，因此该取代基常数也无法预测它们的致突变性。环氧丙烷在液体悬浮试验中的相对致突变性与标准平板掺入试验所测定的不同，并且在两种细菌菌株之间也存在差异。试验差异归因于环氧化物的稳定性。观察到菌株之间的差异是由于仅在TA100中发现的易错修复系统对较强烷基化剂的反应所致。
