Kumar S, Sikka H C, Dubey S K, Czech A, Geddie N, Wang C X, LaVoie E J
Great Lakes Laboratory, State University of New York College, Buffalo 14222.
Cancer Res. 1989 Jan 1;49(1):20-4.
The mutagenic activities of benzo[f]quinoline, benzo[h]quinoline, and a number of their derivatives, including dihydrodiols, K-region oxides, diol epoxides, and tetrahydroepoxides, were assessed in strain TA 100 of Salmonella typhimurium. The dihydrodiol derivatives of benzo[f]quinoline and benzo[h]quinoline were also tested for tumorigenic activity in newborn mice. Benzo[f]quinoline was metabolically activated in the presence of rat liver S-9 preparation to products mutagenic to the bacterial system to a greater extent than was benzo[h]quinoline. However, trans-7,8-dihydro-7,8-dihydroxybenzo[f]quinoline was less mutagenic compared to trans-7,8-dihydroxy-7,8-dihydrobenzo[h]quinoline in the presence of rat liver homogenate. The data on the mutagenic activity of the dihydrodiol derivatives of benzoquinolines were consistent with the intrinsic mutagenicity of the corresponding epoxide derivatives, in that the bay-region diol epoxides and tetrahydroepoxide of benzo[h]quinoline exhibited considerably higher mutagenic activities compared to those of the corresponding derivatives of benzo[f]quinoline at equivalent doses. The K-region oxides of benzo[f]quinoline and benzo[h]quinoline were significantly less mutagenic than their corresponding bay-region diol epoxide and tetrahydroepoxide derivatives. The demonstration that benzo[f]quinoline is significantly more mutagenic than trans-7,8-dihydro-7,8-dihydroxybenzo[f]quinoline, a precursor to the weakly mutagenic bay-region diol epoxide, suggests that the bay-region diol epoxide formation is not the principal pathway for the metabolic activation of benzo[f]quinoline to a mutagen. On the other hand, the isomeric benzo[h]quinoline appears to exert its mutagenic effect via the formation of its bay-region diol epoxide. These results indicate that the position of a nitrogen heteroatom in phenanthrene (the analogous carbocyclic aromatic hydrocarbon) not only has a marked effect on the mutagenic activities of the diol epoxide derivatives, but also can alter the metabolic activation pathways of the parent hydrocarbon. Benzo[f]quinoline, benzo[h]quinoline, and their dihydrodiol derivatives were not tumorigenic in newborn mice.
在鼠伤寒沙门氏菌TA 100菌株中评估了苯并[f]喹啉、苯并[h]喹啉及其一些衍生物（包括二氢二醇、K区域氧化物、二醇环氧化物和四氢环氧化物）的致突变活性。还对苯并[f]喹啉和苯并[h]喹啉的二氢二醇衍生物在新生小鼠中的致瘤活性进行了测试。在大鼠肝脏S-9制剂存在的情况下，苯并[f]喹啉比苯并[h]喹啉在更大程度上被代谢活化为对细菌系统具有致突变性的产物。然而，在大鼠肝脏匀浆存在的情况下，反式-7,8-二氢-7,8-二羟基苯并[f]喹啉与反式-7,8-二羟基-7,8-二氢苯并[h]喹啉相比，致突变性较低。苯并喹啉二氢二醇衍生物的致突变活性数据与相应环氧化物衍生物的固有致突变性一致，即在等效剂量下，苯并[h]喹啉的湾区二醇环氧化物和四氢环氧化物比苯并[f]喹啉的相应衍生物表现出明显更高的致突变活性。苯并[f]喹啉和苯并[h]喹啉的K区域氧化物的致突变性明显低于其相应的湾区二醇环氧化物和四氢环氧化物衍生物。苯并[f]喹啉比弱致突变的湾区二醇环氧化物的前体反式-7,8-二氢-7,8-二羟基苯并[f]喹啉具有明显更高的致突变性，这表明湾区二醇环氧化物的形成不是苯并[f]喹啉代谢活化为致突变物的主要途径。另一方面，异构体苯并[h]喹啉似乎通过其湾区二醇环氧化物的形成发挥其致突变作用。这些结果表明菲（类似的碳环芳烃）中氮杂原子的位置不仅对二醇环氧化物衍生物的致突变活性有显著影响，而且还可以改变母体烃的代谢活化途径。苯并[f]喹啉、苯并[h]喹啉及其二氢二醇衍生物在新生小鼠中不具有致瘤性。
