Kojima M, Degawa M, Hashimoto Y, Tada M
Aichi Cancer Center Research Institute, Nagoya, Japan.
Environ Health Perspect. 1994 Oct;102 Suppl 6(Suppl 6):191-4. doi: 10.1289/ehp.94102s6191.
To elucidate the cause of the difference in genotoxic activity between carcinogenic 3-methoxy-4-aminoazobenzene (3-MeO-AAB) and noncarcinogenic 2-methoxy-4-aminoazobenzene (2-MeO-AAB), we analyzed DNA adducts in the livers of rats exposed to either of these chemicals and studied the resulting biologic potential with the aid of in vitro modified M13 phage DNA. 32P-Postalbeling analysis revealed that the carcinogen 3-MeO-AAB produced 20-fold higher amounts of adducts than did 2-MeO-AAB. Five adducts were formed in the 3-MeO-AAB case whereas only one adduct was apparent in 2-MeO-AAB-treated rat. Studies of in vitro DNA replication using N-hydroxy (N-OH)-aminoazo dye-modified M13 phage DNA as a template demonstrated inhibition by 3-MeO-AAB adducts to be substantially greater than in the 2-MeO-AAB-adducts. The specificity of mutagenesis induced in M13mp9 phage DNA by these chemicals also was analyzed after transfection into SOS-induced Escherichia coli JM103, mutation frequencies being higher with N-OH-3-MeO-AAB- than N-OH-2-MeO-AAB-modified DNA. The mutation spectra differed in each case. Our data suggest that the difference in hepatocarcinogenic activity between the two chemicals depends not only on qualitative and quantitative variation in adduct formation but also on conformation changes in modified DNA.
为阐明致癌性的3-甲氧基-4-氨基偶氮苯（3-MeO-AAB）和非致癌性的2-甲氧基-4-氨基偶氮苯（2-MeO-AAB）之间遗传毒性活性差异的原因，我们分析了暴露于这两种化学物质之一的大鼠肝脏中的DNA加合物，并借助体外修饰的M13噬菌体DNA研究了由此产生的生物学潜能。32P后标记分析显示，致癌物3-MeO-AAB产生的加合物量比2-MeO-AAB高20倍。在3-MeO-AAB处理的情况下形成了五种加合物，而在2-MeO-AAB处理的大鼠中仅有一种加合物明显。使用N-羟基（N-OH）-氨基偶氮染料修饰的M13噬菌体DNA作为模板进行体外DNA复制研究表明，3-MeO-AAB加合物的抑制作用明显大于2-MeO-AAB加合物。将这些化学物质诱导的M13mp9噬菌体DNA中的诱变特异性在转染到SOS诱导的大肠杆菌JM103后也进行了分析，N-OH-3-MeO-AAB修饰的DNA的突变频率高于N-OH-2-MeO-AAB修饰的DNA。每种情况下的突变谱都不同。我们的数据表明，这两种化学物质之间的肝癌致癌活性差异不仅取决于加合物形成的定性和定量变化，还取决于修饰DNA的构象变化。
