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Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals in the invertebrate chordate Ciona intestinalis
Citation:
Nava, G. M., D. Y. Lee, S. Cai, J. L. Boyer, A. Hernández-Zavala, D. J. THOMAS, AND H. R. Gaskins. Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals in the invertebrate chordate Ciona intestinalis . Presented at Experimental Biology 2008, San Diego, CA, April 05 - 09, 2008.
Impact/Purpose:
This abstract describes the capacity of a primitive chordate, Ciona intestinalis, to methylate inorganic arsenic. An orthologous AS3MT gene is expressed in this species. Studies of the function of AS3MT in other species provides clues to the function of this gene in arsenic methylation in humans.
Description:
The biotransformation of inorganic arsenic (iAs) involves methylation by an arsenic (+3 oxidation state) methyltransferase (AS3MT), yielding methyl arsenic (MA), dimethyl arsenic (DMA), and trimethylarsenic (TMA). To identify molecular mechanisms that coordinate arsenic biotransformation, we are using a comparative genomic approach focused on the invertebrate chordate, Ciona intestinalis. Bioinformatic analyses were used to annotate an AS3MT gene in Ciona. RT-PCR analysis from replicate animals demonstrated constitutive expression of AS3MT in branchial sac (BS), gastrointestinal tract (GIT), and heart. Also, replicate animals were exposed to zero (control) or 1 ppm of iAs (as arsenite) in sea water during 24 h or 5 d. Hydride generationatomic absorption spectrometry was used to measure iAs, MA, DMA, and TMA concentrations in BS, GIT, and heart. Methylated metabolites were detected in each of the tissues at both 24 h and 5 d in Ciona specimens exposed to iAs compared with controls (P < 0.01). Average total speciated As concentrations were highest in the BS (3705 ng/g) followed by heart (1019 ng/g) and GIT (835 ng/g) after 5 d. Thus Ciona metabolizes iAs to its methylated metabolites, consistent with the presence of an AS3MT ortholog in its genome, making this basal chordate a useful model to examine the evolution of As detoxification.