Cumulative effects of chromosome aberrations and sister chromatid exchanges in rat liver induced in vivo by heterocyclic amines.
Cumulative effects of chromosome aberrations and sister chromatid exchanges (SCEs) were studied in hepatocytes of F344 rats exposed in vivo to 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) at doses of 12.5, 25 or 50 mg/kg body wt/day or 2-nitro-3-methylimidazo[4,5-f]quinoline (nitro-IQ) at doses of 12.5, 25 or 50 mg/kg body wt/day. Hepatocytes were isolated 24 h after 1, 7, 14 or 28 repeated doses (once a 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 h. Multiple treatment with IQ or nitro-IQ induced significant chromosome aberrations time- and dose-dependently, the maximum frequency of chromosome aberrations in metaphase cells being 39 and 33% respectively, while that in controls was 1.1%. Single treatment with IQ or nitro-IQ induced significant SCEs dose-dependently, the maximum frequency being 0.83 and 0.79 per chromosome respectively, while the control value was 0.51. Multiple treatment with nitro-IQ induced significant SCEs to a plateau level of 0.90 per chromosome. Cytogenetic damage in the liver by IQ was greater than that by nitro-IQ. These results show that this assay of chromosome aberrations and SCEs in rat liver in vivo without partial hepatectomy or mitogen treatment in vivo is a sensitive method for evaluating the cumulative tumor-initiating activities of carcinogenic heterocyclic amines at low doses and should be useful for the detection of unknown hepatocarcinogens.
Sawada
S
S
Department of Drug Safety Research, Eisai Co. Ltd., Gifu-ken, Japan.
Daimon
H
H
Asakura
S
S
Kawaguchi
T
T
Yamatsu
K
K
Furihata
C
C
Matsushima
T
T
D000588:Amines / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002869:Chromosome Aberrations; D006571:Heterocyclic Compounds / Q000633:toxicity*; D008099:Liver / Q000187:drug effects*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012854:Sister Chromatid Exchange
D000588:Amines; D002273:Carcinogens; D006571:Heterocyclic Compounds