Quinoline-induced chromosome aberrations and sister chromatid exchanges in rat liver.
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.
Asakura
S
S
Drug Safety Research Laboratories, Eisai Co., Gifu, Japan.
Sawada
S
S
Sugihara
T
T
Daimon
H
H
Sagami
F
F
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
D011804:Quinolines; D015125:Oxyquinoline; C037219:quinoline