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This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: 27/3/351    most recent 00201.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Lam, S. H. Articles by Gong, Z. Search for Related Content PubMed PubMed Citation Articles by Lam, S. H. Articles by Gong, Z.

Transcriptome kinetics of arsenic-induced adaptive response in zebrafish liver

¹ Department of Biological Sciences, National University of Singapore
² Genome Institute of Singapore, Singapore
³ Institute of Molecular and Cell Biology, Oregon State University, Corvallis, Oregon
⁴ Department of Environmental and Molecular Toxicology and Marine/Freshwater Biomedical Sciences Center, Oregon State University, Corvallis, Oregon

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.

microarray expression profiling; arsenic toxicity; oxidative stress; fish toxicogenomics