Trieff N M, Biagi G L, Sadagopa Ramanujam V M, Connor T H, Cantelli-Forti G, Guerra M C, Bunce H, Legator M S
Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston 77550.
Mol Toxicol. 1989 Winter;2(1):53-65.
The mutagenicity of a series of 19 aromatic amines had been previously measured in Salmonella typhimurium strains TA98 (frame-shift) and TA100 (base-pair) with the addition of S9 from Aroclor 1254-induced rat liver. A quantitative structure-activity relation (QSAR) study using multiple regression analysis points out the influence of three factors on mutagenicity: lipophilic character, position of the amine group, and whether it is free or acetylated, as expressed by log P and two indicator variables I1 and I2, respectively. The multiple regression equations explain 78 and 88% of the variance in log mutagenicity in TA98 and TA100, respectively. First of all, mutagenicity was shown to increase with lipophilicity. On the other hand, mutagenicity is reduced when the amine or acetamido position is ortho to the juncture because of steric hindrance in its biotransformation compared with a non-ortho isomer. It is decreased also by the acetylation of the amine group, probably because the acetyl group needs to be first split off prior to oxidation of the amine group to -NHOH.
先前已在鼠伤寒沙门氏菌TA98菌株（移码突变）和TA100菌株（碱基对突变）中，添加经Aroclor 1254诱导的大鼠肝脏中的S9，测定了一系列19种芳香胺的诱变性。使用多元回归分析的定量构效关系（QSAR）研究指出了三个因素对诱变性的影响：亲脂性、胺基位置以及它是游离的还是乙酰化的，分别用log P和两个指示变量I1和I2表示。多元回归方程分别解释了TA98和TA100中log诱变性差异的78%和88%。首先，诱变性显示出随亲脂性增加而增加。另一方面，由于与非邻位异构体相比其生物转化过程中的空间位阻，当胺基或乙酰氨基位置与连接点邻位时，诱变性会降低。胺基的乙酰化也会使其降低，可能是因为在胺基氧化为 -NHOH之前，乙酰基需要首先被裂解掉。
