Chromosome aberrations, micronuclei and sister-chromatid exchanges (SCEs) in rat liver induced in vivo by hepatocarcinogens including heterocyclic amines.
The induction of chromosome aberrations, micronuclei and SCEs was studied in hepatocytes of F344 rats exposed in vivo to hepatocarcinogens. Hepatocytes were isolated and allowed to proliferate in Williams' medium E supplemented with epidermal growth factor. Cells were fixed after a culture period of 48 h. Oral administration of dimethylnitrosamine at doses of 2.5-20 mg/kg body weight (bw) induced (1) chromosome aberrations in up to 27% of the metaphase cells 2-48 h after its administration, (2) SCEs with a frequency of up to 0.9 per chromosome 2-48 h after its administration, and (3) micronuclei in up to 2.9% of the cells 16-48 h after its administration. Oral administration of 2-acetylaminofluorene at doses of 6.25-200 mg/kg bw induced (1) chromosome aberrations in up to 35% of the metaphase cells after 2-48 h, (2) SCEs at up to 0.9 per chromosome and (3) micronuclei in up to 2.5% of the cells with a maximum after 4 h. Oral administration of CCl4, a non-genotoxic hepatocarcinogen, at a dose of 1600 mg/kg bw did not induce chromosome aberrations, SCEs or micronuclei within 4-72 h. Intraperitoneal injections of Trp-P-1, Glu-P-1, MeIQx, IQ and nitro-IQ resulted in chromosome aberrations in up to 16% of the metaphase cells and SCEs at up to 0.9 per chromosome, while injections of Trp-P-2 and Glu-P-2 produced SCEs at up to 0.7 and 1.1 per chromosome, respectively. The present method of in vivo cytogenetic assay using rats without partial hepatectomy or mitogen treatment in vivo should be useful for evaluating the tumor-initiating activities of hepatocarcinogens.
Sawada
S
S
Department of Drug Safety Research, Eisai Co. Ltd., Gifu-ken, Japan.
Yamanaka
T
T
Yamatsu
K
K
Furihata
C
C
Matsushima
T
T
D000588:Amines / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002469:Cell Separation; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D006571:Heterocyclic Compounds / Q000633:toxicity*; D008099:Liver / Q000187:drug effects*; D008297:Male; D015162:Micronucleus Tests; D051381:Rats; D011916:Rats, Inbred F344; D012854:Sister Chromatid Exchange
D000588:Amines; D002273:Carcinogens; D006571:Heterocyclic Compounds