title: Transcriptome kinetics of arsenic-induced adaptive response in zebrafish liver.
abstract: Arsenic is a prominent environmental toxicant and carcinogen; however, its molecular mechanism of toxicity and carcinogenicity remains poorly understood. In this study, we performed microarray-based expression profiling on liver of zebrafish exposed to 15 parts/million (ppm) arsenic [As(V)] for 8-96 h to identify global transcriptional changes and biological networks involved in arsenic-induced adaptive responses in vivo. We found that there was an increase of transcriptional activity associated with metabolism, especially for biosyntheses, membrane transporter activities, cytoplasm, and endoplasmic reticulum in the 96 h of arsenic treatment, while transcriptional programs for proteins in catabolism, energy derivation, and stress response remained active throughout the arsenic treatment. Many differentially expressed genes encoding proteins involved in heat shock proteins, DNA damage/repair, antioxidant activity, hypoxia induction, iron homeostasis, arsenic metabolism, and ubiquitin-dependent protein degradation were identified, suggesting strongly that DNA and protein damage as a result of arsenic metabolism and oxidative stress caused major cellular injury. These findings were comparable with those reported in mammalian systems, suggesting that the zebrafish liver coupled with the available microarray technology present an excellent in vivo toxicogenomic model for investigating arsenic toxicity. We proposed an in vivo, acute arsenic-induced adaptive response model of the zebrafish liver illustrating the relevance of many transcriptional activities that provide both global and specific information of a coordinated adaptive response to arsenic in the liver.
authors.affiliation: Department of Biological Sciences, National University of Singapore.
authors.forename: Siew Hong
authors.initials: SH
authors.lastname: Lam
authors.forename: Cecilia Lanny
authors.initials: CL
authors.lastname: Winata
authors.forename: Yan
authors.initials: Y
authors.lastname: Tong
authors.forename: Svetlana
authors.initials: S
authors.lastname: Korzh
authors.forename: Wen San
authors.initials: WS
authors.lastname: Lim
authors.forename: Vladimir
authors.initials: V
authors.lastname: Korzh
authors.forename: Jan
authors.initials: J
authors.lastname: Spitsbergen
authors.forename: Sinnakarupan
authors.initials: S
authors.lastname: Mathavan
authors.forename: Lance D
authors.initials: LD
authors.lastname: Miller
authors.forename: Edison T
authors.initials: ET
authors.lastname: Liu
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Gong
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001151:Arsenic / Q000378:metabolism / Q000633:toxicity*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D023281:Genomics; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D020411:Oligonucleotide Array Sequence Analysis; D014158:Transcription, Genetic; D015854:Up-Regulation; D015027:Zebrafish / Q000235:genetics*
chemical_list: D001151:Arsenic