Mersch-Sundermann V, Klopman G, Rosenkranz H S
Department of Environmental Health Sciences, Case Western Reserve University, Cleveland, OH 44106.
Mutat Res. 1992 Jan;265(1):61-73. doi: 10.1016/0027-5107(92)90039-5.
The CASE (computer-automated structure evaluation) methodology was used to investigate the structural basis of the SOS-inducing activity of 56 nitrated polycyclic aromatic hydrocarbons (nitroarenes, nPAH) and the unsubstituted parent PAH molecules. Based upon the presence and/or absence of structural features, CASE identified 5 activating (biophores) and 4 inactivating (biophobes) fragments responsible for the SOS-inducing activity. Based upon these fragments, CASE correctly calculated the genotoxicity of 94.6% of the molecules in the training set (sensitivity = 0.85, specificity = 1.0). Disregarding the questionable experimental results of the unexpected very weak direct-acting activity of the unsubstituted benzo[a]pyrene, dibenzo[a,h]anthracene and 7,12-dimethylbenz[a]anthracene, the concordance of the prediction was 100%, i.e., sensitivity = 1.0, specificity = 1.0. Additionally, the quantitative analysis of the SOS-inducing potency showed a good correlation between the experimental and predicted results. The present analyses indicate an identity in the structural determinants responsible for SOS induction in E. coli PQ37 (SOS chromotest) and mutagenicity in Salmonella typhimurium.
采用CASE（计算机自动化结构评估）方法研究了56种硝化多环芳烃（硝基芳烃，nPAH）和未取代的母体PAH分子的SOS诱导活性的结构基础。基于结构特征的存在与否，CASE识别出了5个负责SOS诱导活性的激活片段（生物活性基团）和4个失活片段（生物失活基团）。基于这些片段，CASE正确计算出了训练集中94.6%分子的遗传毒性（灵敏度 = 0.85，特异性 = 1.0）。不考虑未取代的苯并[a]芘、二苯并[a,h]蒽和7,12 - 二甲基苯并[a]蒽意外的非常弱的直接作用活性的可疑实验结果，预测的一致性为100%，即灵敏度 = 1.0，特异性 = 1.0。此外，SOS诱导效力的定量分析表明实验结果与预测结果之间具有良好的相关性。目前的分析表明，在大肠杆菌PQ37中负责SOS诱导（SOS显色试验）的结构决定因素与鼠伤寒沙门氏菌中的致突变性具有一致性。
