title: Assessment of a twice dosing regimen both before and after partial hepatectomy in the rat liver micronucleus test.
abstract: The liver micronucleus test is an important method to detect in vivo genotoxicants, especially those that require metabolic activation for their genotoxicity. We have already reported that structural or numerical chromosome aberration inducers have to be given before or after partial hepatectomy, respectively, to detect their genotoxicity in the liver of rats. In the present study, we assessed a twice dosing regimen, in which the genotoxicant is dosed both before and after partial hepatectomy, using the four chromosome aberration inducers used in the previous study. Two structural chromosome aberration inducers (diethylnitrosamine and 1,2-dimethylhydrazine) and two numerical chromosome aberration inducers (colchicine and carbendazim) were used. The genotoxicant was administered to 8-week old male F344 rats one day before and again one day after the partial hepatectomy and hepatocytes were isolated 3 days after second dosing (4 days after the partial hepatectomy). As a result, all genotoxicants (structural or numerical chromosome aberration inducers) caused a dose-dependent statistically significant increase in the incidence of micronucleated hepatocytes when given both before and after partial hepatectomy. No marked difference was observed in general toxicity, relative liver weight and cell classification between single dosing regimens and twice dosing regimen of the genotoxicants. These results confirm that the twice dosing regimen, in which the test compound is dosed both before and after partial hepatectomy, can detect in vivo induction of micronucleated hepatocytes by structural or numerical chromosome aberration inducers qualitatively similar to their appropriate regimen in which the test compound is administered either before or after partial hepatectomy.
authors: Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., 1-16-13, Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan. Electronic address: itoh.satoru.n5@daiichisankyo.co.jp.
authors: Satoru
authors: S
authors: Itoh
authors: Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., 1-16-13, Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan.
authors: Miyuki
authors: M
authors: Igarashi
authors: Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., 1-16-13, Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan.
authors: Mayumi
authors: M
authors: Nagata
authors: Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., 1-16-13, Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan.
authors: Chiharu
authors: C
authors: Hattori
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity; D000818:Animals; D001562:Benzimidazoles / Q000633:toxicity; D002219:Carbamates / Q000633:toxicity; D002869:Chromosome Aberrations / Q000139:chemically induced; D003078:Colchicine / Q000633:toxicity; D004052:Diethylnitrosamine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006498:Hepatectomy / Q000379:methods*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D015162:Micronucleus Tests / Q000379:methods; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity*; D011916:Rats, Inbred F344; D013997:Time Factors
chemical_list: D001562:Benzimidazoles; D002219:Carbamates; D009153:Mutagens; D004052:Diethylnitrosamine; C006698:carbendazim; D019813:1,2-Dimethylhydrazine; D003078:Colchicine
keywords: Liver; Micronucleus test; Numerical chromosome aberration; Partial hepatectomy; Structural chromosome aberration