In vivo mutagenesis by the hepatocarcinogen quinoline in the lacZ transgenic mouse: evidence for its in vivo genotoxicity.
Quinoline is carcinogenic to the liver of rats and mice and mutagenic to bacterial tester strains in the presence of rat liver microsomal enzymes. The unscheduled DNA synthesis (UDS) study suggested that quinoline might be a non-genotoxic carcinogen because of the lack of UDS-inducing capacity. In order to determine whether or not cancer induction is initiated by mutagenic DNA lesions, the present study was undertaken to evaluate the mutagenicity of quinoline in an in vivo mutation assay system using the lac Z transgenic mouse (Muta Mouse). Mutation was only induced in the liver, the target organ of carcinogenesis by quinoline, but not in the other organs examined, i.e. lung, kidney and spleen. Mutant frequency in the liver was 4-fold higher than in the untreated control animals. Dimethylnitrosamine, used as a positive control, induced mutation at a frequency 5-fold higher in the liver and 3-fold higher in the spleen than in their respective control organs. It can be concluded that the genotoxicity of quinoline is responsible for its hepatocarcinogenesis, although UDS was not induced under the conditions previously reported.
Suzuki
T
T
Division of Genetics and Mutagenesis, National Institute of Health Sciences, Tokyo, Japan. suzuki@nihs.go.jp
Miyata
Y
Y
Saeki
K
K
Kawazoe
Y
Y
Hayashi
M
M
Sofuni
T
T
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004252:DNA Mutational Analysis; D004128:Dimethylnitrosamine / Q000633:toxicity; D005260:Female; D006498:Hepatectomy; D007763:Lac Operon / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D011804:Quinolines / Q000633:toxicity*; D012156:Reticulocytes / Q000187:drug effects
D002273:Carcinogens; D009153:Mutagens; D011804:Quinolines; C037219:quinoline; D004128:Dimethylnitrosamine