Yamada Katsuya, Suzuki Takayoshi, Kohara Arihiro, Hayashi Makoto, Mizutani Takaharu, Saeki Ken-Ichi
Graduate School of Pharmaceutical Sciences, Nagoya City University, Tanabedori, Mizuho-ku, Nagoya 467-8603, Japan.
Mutat Res. 2004 Apr 11;559(1-2):83-95. doi: 10.1016/j.mrgentox.2003.12.012.
Phenanthrene, a simplest angular polycyclic aromatic hydrocarbon with a bay-region in its molecule, is reported to be non-mutagenic, although most angular (non-linear) polycyclic aromatic hydrocarbons, such as benzo[a]pyrene and chrysene, are known to show genotoxicity after metabolic transformation into a bay-region diol epoxide. On the other hand, benzo[f]quinoline (BfQ), benzo[h]quinoline (BhQ), and 1,7-phenanthroline (1,7-Phe), which are all aza-analogs of phenanthrene, are mutagenic in the Ames test using Salmonella typhimurium TA100 in the presence of a rat liver S9 fraction. In this report, we undertook to investigate the in vivo mutagenicity of BfQ, BhQ and 1,7-Phe by an in vivo mutation assay system using the lacZ transgenic mouse (Muta Mouse). BfQ and BhQ only slightly induced mutation in the liver and lung, respectively. BfQ- and BhQ-induced cII mutant spectra showed no characteristics compared with that of the control. These results suggest that the in vivo mutagenicities of BfQ and BhQ were equivocal. On the other hand, 1,7-Phe induced a potent mutation in the liver and a weak mutation in the lung. Furthermore 1,7-Phe depressed the G:C to A:T transition and increased the G:C to C:G transversion in the liver like quinoline, a hepatomutagen possessing the partial structure of 1,7-Phe, compared with the spontaneous mutation spectrum. These results suggest that the in vivo mutagenicity of 1,7-Phe might be caused by the same mechanism as that of quinoline, which induced the same mutational spectrum change (G:C to C:G transversion).
菲是一种最简单的角型多环芳烃，其分子中存在湾区。据报道，它没有致突变性，尽管大多数角型（非直线型）多环芳烃，如苯并[a]芘和 Chrysene，在代谢转化为湾区二醇环氧化物后具有遗传毒性。另一方面，苯并[f]喹啉（BfQ）[h]喹啉（BhQ）和 1,7 - 菲咯啉（1,7 - Phe），它们都是菲的氮杂类似物，在有大鼠肝脏 S9 组分存在的情况下，使用鼠伤寒沙门氏菌 TA100 进行的艾姆斯试验中具有致突变性。在本报告中，我们通过使用 lacZ 转基因小鼠（Muta Mouse）的体内突变检测系统，研究了 BfQ、BhQ 和 1,7 - Phe 的体内致突变性。BfQ 和 BhQ 分别仅在肝脏和肺中轻微诱导突变。与对照组相比，BfQ 和 BhQ 诱导的 cII 突变谱没有特征。这些结果表明，BfQ 和 BhQ 的体内致突变性不明确。另一方面，1,7 - Phe 在肝脏中诱导强烈突变，在肺中诱导微弱突变。此外，与自发突变谱相比，1,7 - Phe 在肝脏中降低了 G:C 到 A:T 的转换，并增加了 G:C 到 C:G 的颠换，类似于喹啉，一种具有 1,7 - Phe 部分结构的肝诱变剂。这些结果表明，1,7 - Phe 的体内致突变性可能是由与喹啉相同的机制引起的，喹啉诱导了相同的突变谱变化（G:C 到 C:G 颠换）。
