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Comparison of the mutagenicity of aristolochic acid I and aristolochic acid II in the gpt delta transgenic mouse kidney

文献类型：期刊论文

作者Xing, Guozhen1,2; Qi, Xinming1; Chen, Min1,2; Wu, Yuanfeng1,2; Yao, Jun1,2; Gong, Likun1; Nohmi, Takehiko3; Luan, Yang1; Ren, Jin1
刊名MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
出版日期2012-03-18
卷号743期号:1-2页码:52-58
ISSN号1383-5718
关键词Aristolochic acid DNA adducts Mutagenesis
DOI10.1016/j.mrgentox.2011.12.021
文献子类Article
英文摘要Aristolochic acid (AA) is known to be a potent mutagen and carcinogen. Aristolochic acid I (AAI) and aristolochic acid II (AAII), the two major components of AA, differ from each other by a single methoxy group. However, their individual mutagenic characteristics in vivo are unclear. In the present study, we compared their DNA adduct formation and mutagenicities in the gpt delta transgenic mouse kidney. The dA-AAI, dG-AAI, dA-AAII and dG-AAII were identified in the kidney two days after intragastric administration of AAI or AAII at 5 mg/kg. The concentration of DNA adducts formed by AAII was approximately 2.5-fold higher than that formed by AII (p < 0.05). The mutant frequency induced by AAII was nearly two-fold higher than that induced by AAI (p <0.05) following administration of 5 mg/kg AAI or AAII, five times per week for six weeks. Investigation of the mutation spectra showed no statistically significant difference between AAI- and AAII-treated mice (p>0.05). A:T to T:A transversion was the predominant type of mutation in both treated groups, the GC-associated mutation rates, however, differed between the AAI and AAII treatments. The in vivo metabolic pathways of AAI and AAII are different, and this may affect their mutagenicity. In the present study, we measured the levels of AAI and AAII in the kidney and plasma of gpt delta transgenic mice at multiple time points after a single intragastric dose of 1 or 5 mg/kg of either component. Our results showed that the levels of AAII in both kidney and plasma were considerably higher than those of AAI (p<0.01). The present study indicated that AAII showed more carcinogenic risk than AAI in vivo, and this may be, at least partly, the result of its increased levels in kidney and plasma. (C) 2012 Elsevier B.V. All rights reserved.
WOS关键词DNA ADDUCT FORMATION ; IONIZATION-MASS-SPECTROMETRY ; LIQUID-CHROMATOGRAPHY ; SALMONELLA-TYPHIMURIUM ; METABOLIC-ACTIVATION ; CHINESE HERBS ; RAT-KIDNEY ; LIVER ; NEPHROPATHY ; MUTATIONS
资助项目National Grand Fundamental Research 973 Program of China[2006CB504700] ; Key Projects of National Science and Technology Pillar Program[2008ZX09305-007] ; Key Projects of National Science and Technology Pillar Program[2009ZX09501-033] ; National Natural Scientific Foundation of China[21077112]
WOS研究方向Biotechnology & Applied Microbiology ; Genetics & Heredity ; Toxicology
语种英语
出版者ELSEVIER SCIENCE BV
WOS记录号WOS:000301966600007
源URL[http://119.78.100.183/handle/2S10ELR8/278148]  
专题药物安全性评价中心
通讯作者Luan, Yang
作者单位1.Chinese Acad Sci, Ctr Drug Safety & Evaluat Res, State Key Lab New Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
2.Chinese Acad Sci, Grad Sch, Shanghai 201203, Peoples R China;
3.Natl Inst Hlth Sci, Div Genet & Mutagenesis, Tokyo 1588501, Japan
推荐引用方式
GB/T 7714		 Xing, Guozhen,Qi, Xinming,Chen, Min,et al. Comparison of the mutagenicity of aristolochic acid I and aristolochic acid II in the gpt delta transgenic mouse kidney[J]. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS,2012,743(1-2):52-58.
APA Xing, Guozhen.,Qi, Xinming.,Chen, Min.,Wu, Yuanfeng.,Yao, Jun.,...&Ren, Jin.(2012).Comparison of the mutagenicity of aristolochic acid I and aristolochic acid II in the gpt delta transgenic mouse kidney.MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS,743(1-2),52-58.
MLA Xing, Guozhen,et al."Comparison of the mutagenicity of aristolochic acid I and aristolochic acid II in the gpt delta transgenic mouse kidney".MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 743.1-2(2012):52-58.

入库方式： OAI收割

来源：上海药物研究所

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