Evaluation of the repeated dose liver micronucleus assay using young adult rats with cyclophosphamide monohydrate: a report of a collaborative study by CSGMT/JEMS.MMS
| Autor: | Kazuyo Zaizen, Hisao Ishida, Kazumi Matsumoto, Atsushi Miyamoto, Kazufumi Kawasako, Yumi Wako |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Societies Pharmaceutical Reticulocytes Health Toxicology and Mutagenesis Repeated dosing Administration Oral Biology Pharmacology Drug Administration Schedule Rats Sprague-Dawley Japan Bone Marrow Genetics medicine Animals Humans Dosing Young adult Cooperative Behavior Cyclophosphamide Carcinogen Chromosome Aberrations Micronucleus Tests Dose-Response Relationship Drug Body Weight Age Factors Rats medicine.anatomical_structure Liver Organ Specificity Micronucleus test Carcinogens Hepatocytes Bone marrow Micronucleus Cyclophosphamide Monohydrate |
| Zdroj: | Mutation research. Genetic toxicology and environmental mutagenesis. |
| ISSN: | 1879-3592 |
| Popis: | The repeated dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect liver carcinogens, and this assay could be integrated into general toxicological studies. In this study, in order to assess the performance of the assay, cyclophosphamide monohydrate (CP) was tested in a 14-day RDLMN assay. Based on the results of the 4-day repeated dose-finding study, 10 mg/kg/day of CP was selected as the highest dose and the lower doses were set at 5, 2.5, 1.25, and 0.625 mg/kg/day for the 14-day RDLMN assay. On the day after the completion of the dosing period, specimens of hepatocytes and bone marrow cells were prepared and the induction of micronuclei was assessed. No changes were observed in the incidences of micronucleated hepatocytes. Nevertheless, the incidences of micronucleated immature erythrocytes in the bone marrow were increased significantly at CP doses of 1.25 mg/kg/day or more. These findings are consistent with reports that CP induces tumors in various tissues but it does not induce liver tumors. |
| Databáze: | OpenAIRE |
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