title: Quinoline-induced chromosome aberrations and sister chromatid exchanges in rat liver.
abstract: Induction of chromosome aberrations and sister chromatid exchanges (SCEs) was studied in hepatocytes of F344 rats exposed in vivo to the hepatocarcinogen quinoline (Q). Hepatocytes were isolated 4-48 hr after a single dose of 200 mg/kg body weight or 24 hr after 28 repeated doses (once a day) of 25-200 mg/kg body weight/day by gastric intubation, and allowed to proliferate in Williams' medium E supplemented with epidermal growth factor. Cells were fixed after a culture period of 48 hr. A single dose of Q induced chromosome aberrations in up to 22% of metaphase cells, and SCEs with a frequency of up to 1.27 per chromosome 12 hr after the dose, while the control values were 1% and 0.63 per chromosome, respectively. Treatment with 28 repeated doses of Q induced significant chromosome aberrations and SCEs dose-dependently. Cytogenetic damage induced induced in the liver by repeated doses of Q was greater than induced by a single dose. Furthermore, Q induced replicative DNA synthesis in the liver, but failed to induce micronucleus formation in the bone marrow. The noncarcinogen 8-hydroxyquinoline was also examined and found to be essentially non-genotoxic to rat liver. These results show that Q is a genotoxic carcinogen to rat liver and the present method of in vivo cytogenetic assay should be useful for evaluating the genotoxicity of hepatocarcinogens.
authors.affiliation: Drug Safety Research Laboratories, Eisai Co., Gifu, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Asakura
authors.forename: S
authors.initials: S
authors.lastname: Sawada
authors.forename: T
authors.initials: T
authors.lastname: Sugihara
authors.forename: H
authors.initials: H
authors.lastname: Daimon
authors.forename: F
authors.initials: F
authors.lastname: Sagami
mesh_terms: D000818:Animals; D002869:Chromosome Aberrations; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D015162:Micronucleus Tests; D015125:Oxyquinoline / Q000633:toxicity*; D011804:Quinolines / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012854:Sister Chromatid Exchange
chemical_list: D011804:Quinolines; D015125:Oxyquinoline; C037219:quinoline