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J.Health Sci., 53(4), 470-474, 2007
Clastogenicity of Quinoline Derivatives in the Liver Micronucleus Assay Using Rats and Mice
Atsushi Hakura,a Minoru Kadoi,b
Takayoshi Suzuki,c and Ken-ichi Saeki*, b
aDrug Safety Research Laboratories, Eisai Co., Ltd., 1 Kawashimatakehaya-machi, Kakamigahara, Gifu, 501-6195, Japan,
bGraduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabedori, Mizuho-ku, Nagoya 467-8603, Japan, and
cDivision of Cellular and Gene Therapy Products, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Induction of micronucleated liver cells (MN-liver cells) was examined with the hepatocarcinogenic quinoline and its fluorinated derivatives, 3-fluoroquinoline (3-FQ) and 5-fluoroquinoline (5-FQ), using non-hepatectomized rats and mice. Male F344 rats or ICR mice were given each test chemical at a daily dose of 0.5 mmol/kg for three consecutive days by i.p. injection, and sacrificed at six or eleven days after the final treatment. The data may suggest that the induction frequencies of MN-liver cells by the quinoline derivatives correlate with the magnitudes of both their medium-term carcinogenicity and bacterial mutagenicity. Thus, the potently hepatocarcinogenic/mutagenic 5-FQ caused significantly higher levels of induction of MN-liver cells than the vehicle in both rats and mice. The non-hepatocarcinogenic/non-mutagenic 3-FQ showed no appreciable differences in MN-liver cell induction from the control group in rats and mice. Quinoline showed a slight and statistically insignificant increase of MN-liver cells in mice, but there was not such increase in rats. These findings may suggest the utility of the micronucleus test using hepatocytes from non-hepatectomized animals, although its sensitivity may be low as compared with hepatectomized animals.
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