title: Antimutagenic structural modification of quinoline assessed by an in vivo mutagenesis assay using lacZ-transgenic mice.
abstract: Quinoline, a hepatocarcinogen, mutates the bacterial tester strains in the presence of the rat liver microsomal enzymes and induces GST-P (placental glutathione S-transferase)-positive foci in a medium-term bioassay system for hepatocarcinogenesis. On the other hand, 3-fluorinated quinoline was neither mutagenic nor carcinogenic in the same assay systems, whereas, 5-fluoroquinoline was mutagenic and carcinogenic. Quinoline was recently demonstrated to be mutagenic in an in vivo mutagenicity assay system using the lacZ-transgenic mouse (MutaMouse). The present study was undertaken to know whether 3-fluoroquinoline would be devoid of in vivo mutagenicity in MutaMouse. Quinoline and 5-fluoroquinoline were also tested in the same system. Mutagenicity was evaluated in the liver, the target organ of quinoline carcinogenesis, and also in the bone marrow and testis. The results strongly indicate that fluorine-substitution at the position-3 of quinoline could be an anti-genotoxic structural modification of quinoline in a wide range of its genotoxic end-points.
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabedori, Mizuho-ku, Nagoya 467, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Miyata
authors.forename: K
authors.initials: K
authors.lastname: Saeki
authors.forename: Y
authors.initials: Y
authors.lastname: Kawazoe
authors.forename: M
authors.initials: M
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Sofuni
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000648:ultrastructure; D007763:Lac Operon; D008099:Liver / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D011804:Quinolines / Q000737:chemistry* / Q000633:toxicity*; D013737:Testis / Q000648:ultrastructure
chemical_list: D011804:Quinolines; C037219:quinoline; C082974:3-fluoroquinoline