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学科主题: 公共卫生
题名:
In vitro genotoxicity of danthron and its potential mechanism
作者: Zhang, Zhaohui; Fu, Juanling; Yao, Biyun; Zhang, Xiaolin; Zhao, Peng; Zhou, Zongcan
关键词: Danthron ; 1,8-Dihydroxyanthraquinone ; Mutagenicity ; DT-diaphorase ; Oxidative stress
刊名: MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
发表日期: 2011-05-18
DOI: 10.1016/j.mrgentox.2011.02.006
卷: 722, 期:1, 页:39-43
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biotechnology & Applied Microbiology ; Genetics & Heredity ; Toxicology
研究领域[WOS]: Biotechnology & Applied Microbiology ; Genetics & Heredity ; Toxicology
关键词[WOS]: TOPOISOMERASE-II ; MAMMALIAN-CELLS ; ANTHRAQUINONES ; LIVER ; MUTAGENICITY ; TOXICOLOGY ; STRAINS ; TA102 ; ASSAY
英文摘要:

To ascertain the in vitro genotoxicity of danthron and its potential mechanism of action, we performed an Ames test, a cytokinesis-block micronucleus assay and a comet assay in Balb/c 3T3 cells. The Ames test revealed that danthron was mutagenic only toward Salmonella typhimurium strain TA102 in the presence of an exogenous metabolic activation system (S9 mix). Danthron (25,50 and 10011 mu g/ml) increased the frequencies of micronuclear cells with or without S9 mix, and the comet length, tail length and Olive tail moment in comet assays without S9 mix in a dose-dependent manner. These results demonstrated the in vitro genotoxicity of danthron and that 3T3 cells are capable of activating danthron. When NADP was replaced by MAD in the S9 mix, danthron remained mutagenic toward strain TA102. The addition of dicoumarol, a DT-diaphorase inhibitor, decreased the number of danthron-induced histidine revertants by 35-39%, indicating that DT-diaphorase is involved in the metabolic activation of danthron in the presence of NADH as an electron donor. In 3T3 cells, increases in reactive oxygen species (ROS) formation and 8-hydroxydeoxyguanosine levels as well as a reduction in GSH levels were induced by danthron in a dose-dependent manner, indicating that oxidative stress may be a major contributing pathway in the genotoxicity of danthron. (C) 2011 Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: 2002CB12906
项目资助者: China National Key Basic Research and Development Program
WOS记录号: WOS:000291913600005
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61297
Appears in Collections:北京大学公共卫生学院_毒理学系_期刊论文

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作者单位: Peking Univ, Dept Toxicol, Hlth Sci Ctr, Beijing 100191, Peoples R China

Recommended Citation:
Zhang, Zhaohui,Fu, Juanling,Yao, Biyun,et al. In vitro genotoxicity of danthron and its potential mechanism[J]. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS,2011,722(1):39-43.
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