The 14-day repeated dose liver micronucleus test with methapyrilene hydrochloride using young adult rats

被引：4
作者：
Inoue, Kenji [1 ]
Ochi, Akimu [1 ]
Koda, Akira [1 ]
Wako, Yumi [2 ]
Kawasako, Kazufumi [2 ]
Doi, Takaaki [1 ]
机构：
[1] Maruho Co Ltd, Chudoji, Kyoto 6008815, Japan
[2] LSI Medience Corp, Kamisu, Ibaraki 3140255, Japan
来源：
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS | 2015年 / 780卷
关键词：
Liver micronucleus assay; Methapyrilene hydrochloride; Rat; Repeated-dose toxicity study; Hepatocarcinogen; Integration; POTENT HEPATOCARCINOGEN METHAPYRILENE; ASSAY; TOXICITY; MUTATION; CARCINOGENICITY; GENOTOXICITY; CHEMICALS; CELLS;
D O I：
10.1016/j.mrgentox.2014.04.004
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
The repeated dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect genotoxic hepatocarcinogens that can be integrated into a general toxicity study. The assay methods were thoroughly validated by 19 Japanese facilities. Methapyrilene hydrochloride (MP), known to be a non-genotoxic hepatocarcinogen, was examined in the present study. MP was dosed orally at 10,30 and 100 mg/kg/day to 6-week-old male Crl:CD (SD) rats daily for 14 days. Treatment with MP resulted in an increase in micronucleated hepatocytes (MNHEPs) with a dosage of only 100 mg/kg/day. At this dose level, cytotoxicity followed by regenerative cell growth was noted in the liver. These findings suggest that MP may induce clastogenic effects indirectly on the liver or hepatotoxicity of MP followed by regeneration may cause increase in spontaneous incidence of MNHEPs. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码：123 / 127
页数：5
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