In vivo mutagenicity of benzo[f]quinoline, benzo[h]quinoline, and 1,7-phenanthroline using the lacZ transgenic mice.
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).
Yamada
Katsuya
K
Graduate School of Pharmaceutical Sciences, Nagoya City University, Tanabedori, Mizuho-ku, Nagoya 467-8603, Japan.
Suzuki
Takayoshi
T
Kohara
Arihiro
A
Hayashi
Makoto
M
Mizutani
Takaharu
T
Saeki
Ken-Ichi
K
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D007763:Lac Operon / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008956:Models, Chemical; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000187:drug effects*; D009152:Mutagenicity Tests; D009154:Mutation / Q000235:genetics; D010618:Phenanthrolines / Q000378:metabolism / Q000633:toxicity*; D011804:Quinolines / Q000378:metabolism / Q000633:toxicity*; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics; D014764:Viral Proteins
D017931:DNA Primers; D010618:Phenanthrolines; D011804:Quinolines; D014157:Transcription Factors; D014764:Viral Proteins; C039000:cII protein, bacteriophage lambda; C039107:benzo(h)quinoline; C053486:1,7-phenanthroline; C039108:benzo(f)quinoline