Skip Navigation



ToxSci Advance Access published online on October 15, 2009
Toxicological Sciences, doi:10.1093/toxsci/kfp250
This Article
Right arrow Advance Access manuscript (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Thomas, D. J.
Right arrow Articles by Gaskins, H. R.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Thomas, D. J.
Right arrow Articles by Gaskins, H. R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2009. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Arsenic (+3 Oxidation State) Methyltransferase and the Methylation of Arsenicals in the Invertebrate Chordate Ciona intestinalis

David J. Thomas*,||, Gerardo M. Nava{dagger}, Shi-Ying Cai{ddagger},§, James L. Boyer{ddagger},§, Araceli Hernández-Zavala and H. Rex Gaskins{dagger},{ddagger},||

* Pharmacokinetics Branch, Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711 {dagger} University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 {ddagger} Mt. Desert Island Biological Laboratory, Salisbury Cove, ME 04672 § Liver Center, Yale University School of Medicine, New Haven, CT 06519 Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599

|| To whom correspondence should be addressed. E-mail: thomas.david{at}epa.gov or hgaskins{at}illinois.edu.

Received June 8, 2009; revision received September 1, 2009; accepted October 1, 2009


  Abstract

Biotransformation of inorganic arsenic (iAs) involves methylation catalyzed by arsenic (+3 oxidation state) methyltransferase (As3mt), yielding mono- , di- , and trimethylated arsenicals. To investigate the evolution of molecular mechanisms that mediate arsenic biotransformation, a comparative genomic approach focusing on the invertebrate chordate Ciona intestinalis, was used. Bioinformatic analyses identified an As3mt gene in the C. intestinalis genome. Constitutive As3mt RNA expression was observed in heart, branchial sac and gastrointestinal tract. Adult animals were exposed to zero or 1 ppm of iAs for 1 or 5 days. Steady-state As3mt RNA expression in the gastrointestinal tract was not modulated significantly by 5 days of exposure to iAs. Tissue levels of iAs and its methylated metabolites were determined by hydride generation-cryotrapping-gas chromatography-atomic absorption spectrometry. At either time point, exposure to iAs significantly increased concentrations of iAs and its methylated metabolites in tissues. After 5 days of exposure, total speciated arsenic concentrations were highest in branchial sac (3705 ng/g) followed by heart (1019 ng/g) and gastrointestinal tract (835 ng/g). At this time point, the sum of the speciated arsenical concentrations in gastrointestinal tract and heart equaled or exceeded that of iAs; in branchial sac, iAs was the predominant species present. Ciona intestinalis metabolizes iAs to its methylated metabolites, which are retained in tissues. This metabolic pattern is consistent with the presence of an As3mt ortholog in its genome and constitutive expression of the gene in prominent organs, making this basal chordate a useful model to examine the evolution of arsenic detoxification.

Key Words: arsenic; Ciona intestinalis; comparative genomics; methyltransferases; toxicogenomics.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.