title: RNA sequencing provides insights into the toxicogenomic response of ZF4 cells to methyl methanesulfonate.
abstract: 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 639.16 ± 61.8 µm, and apoptosis was induced within 24 h 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.
authors.affiliation: State Key Laboratory of Fresh water Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, 7 Southern East Lake Road, Wuhan, 430072, People's Republic of China.|University of Chinese Academy of Sciences, Yuquan Road 19A, Beijing, 100039, People's Republic of China.
authors.forename: Zhouquan
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Fresh water Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, 7 Southern East Lake Road, Wuhan, 430072, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Long
authors.affiliation: State Key Laboratory of Fresh water Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, 7 Southern East Lake Road, Wuhan, 430072, People's Republic of China.|University of Chinese Academy of Sciences, Yuquan Road 19A, Beijing, 100039, People's Republic of China.
authors.forename: Liqiao
authors.initials: L
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Fresh water Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, 7 Southern East Lake Road, Wuhan, 430072, People's Republic of China.
authors.forename: Guili
authors.initials: G
authors.lastname: Song
authors.affiliation: State Key Laboratory of Fresh water Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, 7 Southern East Lake Road, Wuhan, 430072, People's Republic of China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Fresh water Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, 7 Southern East Lake Road, Wuhan, 430072, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Fresh water Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, 7 Southern East Lake Road, Wuhan, 430072, People's Republic of China.
authors.forename: Zongbin
authors.initials: Z
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Fresh water Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, 7 Southern East Lake Road, Wuhan, 430072, People's Republic of China.
authors.forename: Heping
authors.initials: H
authors.lastname: Dai
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D008741:Methyl Methanesulfonate / Q000633:toxicity*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D043922:Toxicogenetics; D059467:Transcriptome; D015027:Zebrafish
chemical_list: D008741:Methyl Methanesulfonate
keywords: RNA-seq; ZF4; environmental health risk assessment; methyl methanesulfonate; toxicogenomics; zebrafish