Hepatocarcinogen quinoline induces G:C to C:G transversions in the cII gene in the liver of lambda/lacZ transgenic mice (MutaMouse).
Quinoline is carcinogenic to the liver in rodents, but it is not clear whether it acts by a genotoxic mechanism. We previously demonstrated that quinoline does induce gene mutation in the liver of lambda/lacZ transgenic mice. In the present report, we reveal the molecular nature of the mutations induced by quinoline in the lambda cII gene, which is also a phenotypically selectable marker in the lambda transgene. (The cII gene has 294bp, which enables much easier sequence analysis than the original lacZ gene (3kb)). The liver cII mutant frequency was nine times higher in quinoline-treated mice than in control mice. Sequence analysis revealed that quinoline induced primarily G:C to C:G transversions (25 of 34). Thus, we have confirmed that quinoline is genotoxic in its target organ, and the G:C to C:G transversion is the molecular signature of quinoline-induced mutations.
Suzuki
T
T
Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158, Japan. suzuki@nihs.go.jp
Wang
X
X
Miyata
Y
Y
Saeki
K
K
Kohara
A
A
Kawazoe
Y
Y
Hayashi
M
M
Sofuni
T
T
D000818:Animals; D010582:Bacteriophage lambda / Q000235:genetics; D001483:Base Sequence; D002273:Carcinogens / Q000633:toxicity*; D017931:DNA Primers / Q000235:genetics; D004274:DNA, Recombinant / Q000235:genetics; D007763:Lac Operon; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D011804:Quinolines / Q000633:toxicity*; D012854:Sister Chromatid Exchange / Q000187:drug effects / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014764:Viral Proteins
D002273:Carcinogens; D017931:DNA Primers; D004274:DNA, Recombinant; D011804:Quinolines; D014157:Transcription Factors; D014764:Viral Proteins; C039000:cII protein, bacteriophage lambda; C037219:quinoline