title: Transcriptome profiling and pathway analysis of hepatotoxicity induced by tris (2-ethylhexyl) trimellitate (TOTM) in mice.
abstract: Tris (2-ethylhexyl) trimellitate (TOTM) is commonly used as an alternative plasticizer for medical devices. But very little information was available on its biological effects. In this study, we investigated toxicity effects of TOTM on hepatic differential gene expression analyzed by using high-throughput sequencing analysis for over-represented functions and phenotypically anchored to complementary histopathologic, and biochemical data in the liver of mice. Among 1668 candidate genes, 694 genes were up-regulated and 974 genes were down-regulated after TOTM exposure. Using Gene Ontology analysis, TOTM affected three processes: the cell cycle, metabolic process and oxidative activity. Furthermore, 11 key genes involved in the above processes were validated by real time PCR. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that these genes were involved in the cell cycle pathway, lipid metabolism and oxidative process. It revealed the transcriptome gene expression response to TOTM exposure in mouse, and these data could contribute to provide a clearer understanding of the molecular mechanisms of TOTM-induced hepatotoxicity in human.
authors.affiliation: Key Laboratory for Medical Device Safety Evaluation and Research, Zhejiang Institute of Medical Device Supervision and Testing, Hangzhou 310018, China.
authors.forename: Xian-Hua
authors.initials: XH
authors.lastname: Chen
authors.affiliation: Key Laboratory for Medical Device Safety Evaluation and Research, Zhejiang Institute of Medical Device Supervision and Testing, Hangzhou 310018, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Yi-Xiang
authors.initials: YX
authors.lastname: Hu
authors.affiliation: Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Dan-Xian
authors.initials: DX
authors.lastname: Wang
authors.affiliation: Key Laboratory for Medical Device Safety Evaluation and Research, Zhejiang Institute of Medical Device Supervision and Testing, Hangzhou 310018, China.
authors.forename: Li
authors.initials: L
authors.lastname: Fang
authors.affiliation: Key Laboratory for Medical Device Safety Evaluation and Research, Zhejiang Institute of Medical Device Supervision and Testing, Hangzhou 310018, China.
authors.forename: Xue-Lai
authors.initials: XL
authors.lastname: Li
authors.affiliation: Key Laboratory for Medical Device Safety Evaluation and Research, Zhejiang Institute of Medical Device Supervision and Testing, Hangzhou 310018, China.
authors.forename: Jin-Chuan
authors.initials: JC
authors.lastname: Zhao
authors.affiliation: Key Laboratory for Medical Device Safety Evaluation and Research, Zhejiang Institute of Medical Device Supervision and Testing, Hangzhou 310018, China.
authors.forename: Hai-Rong
authors.initials: HR
authors.lastname: Yu
authors.affiliation: Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Hua-Zhong
authors.initials: HZ
authors.lastname: Ying
authors.affiliation: Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China. Electronic address: yuchenhuan2002@163.com.
authors.forename: Chen-Huan
authors.initials: CH
authors.lastname: Yu
mesh_terms: D000818:Animals; D001565:Benzoates / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D010084:Oxidation-Reduction / Q000187:drug effects; D010968:Plasticizers / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001565:Benzoates; D010968:Plasticizers; C034367:trioctyl trimellitate
keywords: Cell cycle; Cytochrome P450; Digital gene expression profiling; Lipid metabolism; Oxidative process