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题名: RNA sequencing provides insights into the toxicogenomic response of ZF4 cells to methyl methanesulfonate
作者: Li, Zhouquan1, 2; Long, Yong1; Zhong, Liqiao1, 2; Song, Guili1; Zhang, Xiaohua1; Yuan, Li1; Cui, Zongbin1; Dai, Heping1
关键词: zebrafish ; ZF4 ; RNA-seq ; toxicogenomics ; environmental health risk assessment ; methyl methanesulfonate
刊名: JOURNAL OF APPLIED TOXICOLOGY
发表日期: 2016
DOI: 10.1002/jat.3147
卷: 36, 期:1, 页:94-104
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
类目[WOS]: Toxicology
研究领域[WOS]: Toxicology
英文摘要: Whole genome transcriptomic studies are powerful for characterizing the molecular mechanisms underlying the physiological effects of chemicals, and are informative for environmental health risk assessment. Alkylating agents are an abundant class of chemicals that can damage DNA in the environment, and are used for anticancer treatments. Currently, little is known regarding the molecular mechanisms of toxic alkylating agents in zebrafish cell lines. In this study, RNA-sequencing was used to investigate the transcriptomic responses of zebrafish ZF4 cells following exposure to the model genotoxicant methyl methanesulfonate (MMS). The half-maximal inhibitory concentration (IC50) of MMS was 639.1661.8 mu m, and apoptosis was induced within 24h of exposure. RNA sequencing identified 3601 differentially expressed genes (DEGs) that were upregulated and 3037 that were downregulated. Gene ontology enrichment analysis revealed that most DEGs belonged to synthesis and metabolism categories. RNA-associated processes were the most upregulated, while cell cycle and adhesion were the most repressed processes, and neuron-related processes were the most downregulated developmental process. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis identified DNA damage repair, cell cycle, apoptosis and spliceosome as overrepresented terms. Six types of alternative splicing were detected. In total, 1156 alternative splicing DEGs were specifically expressed following MMS treatment, many of which belonged to metabolism and catabolic process categories. Cluster analysis of orthologs was able to extrapolate toxicotranscriptomic data between zebrafish and yeast. These results provide insight into the genome-wide response of ZF4 cells following exposure to MMS, and this knowledge will inform future toxicogenomic data analysis and environmental health risk assessment. Copyright (c) 2015 John Wiley & Sons, Ltd.
关键词[WOS]: DIFFERENTIALLY EXPRESSED GENES ; DNA-POLYMERASE-BETA ; SACCHAROMYCES-CEREVISIAE ; EXCISION-REPAIR ; STRAND BREAKS ; SEQ DATA ; YEAST ; NETWORKS ; DAMAGE ; ENVIRONMENT
语种: 英语
项目资助者: Natural Science Foundation of China(21037004) ; State Key Laboratory of Fresh Water Ecology and Biotechnology(2011FBZ10)
WOS记录号: WOS:000365795900009
ISSN号: 0260-437X
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/27458
Appears in Collections:水生生物分子与细胞生物学研究中心_期刊论文

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作者单位: 1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Fresh Water Ecol & Biotechnol, Wuhan 430072, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100039, Peoples R China
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