In vitro genotoxicity of danthron and its potential mechanism

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...

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Veröffentlicht in:Mutation research 2011-05, Vol.722 (1), p.39-43
Hauptverfasser: Zhang, Zhaohui, Fu, Juanling, Yao, Biyun, Zhang, Xiaolin, Zhao, Peng, Zhou, Zongcan
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Fu, Juanling
Yao, Biyun
Zhang, Xiaolin
Zhao, Peng
Zhou, Zongcan
description 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 100μg/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 NAD 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.
doi_str_mv 10.1016/j.mrgentox.2011.02.006
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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.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>21354327</pmid><doi>10.1016/j.mrgentox.2011.02.006</doi><tpages>5</tpages></addata></record>
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subjects 1,8-Dihydroxyanthraquinone
Animals
Anthraquinones - metabolism
Anthraquinones - toxicity
BALB 3T3 Cells
Bioassays
Biological and medical sciences
Biotransformation
Comet Assay
Cytokines
Danthron
Dicumarol - pharmacology
Dose-Response Relationship, Drug
DT-diaphorase
Fundamental and applied biological sciences. Psychology
Genetics of eukaryotes. Biological and molecular evolution
Medical sciences
Metabolism
Mice
Micronucleus Tests
Mutagenesis
Mutagenicity
Mutagenicity Tests
Mutagens - toxicity
NAD(P)H Dehydrogenase (Quinone) - metabolism
NADP - chemistry
Olea
Oxidative Stress
Salmonella
Salmonella typhimurium
Salmonella typhimurium - genetics
Toxicity
Toxicology
title In vitro genotoxicity of danthron and its potential mechanism
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