EPA Science Inventory

*Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals in the invertebrate chordate ciona intestinalis

Citation:

THOMAS, D. J., G. Nava, S. Cai, J. L. Boyer, A. Hernandez-Zavala, AND R. Gaskins. *Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals in the invertebrate chordate ciona intestinalis. TOXICOLOGICAL SCIENCES. Society of Toxicology, 113(1):70-76, (2010).

Description:

Biotransformation of inorganic arsenic (iAs) involves methylation catalyzed by arsenic (+3 oxidation state) methyltransferase (As3mt) , yielding mono-, di-, and trimethylated arsenicals. A comparative genomic approach focused on Ciona intestinaJis, an invertebrate chordate, was used to explore the evolution of molecular mechanisms that mediate arsenic biotransformation. Bioinformatic analyses identified an As3mt gene in the C. intestinaJis genome. Adult animals were exposed to zero or 1 ppm of iAs for 1 or 5 days. Tissue levels of iAs and its methylated metabolites were determined by hydride generation-cryotrapping-gas chromatography-atomic absorption spectrometry. In silico cloning demonstrated the presence of As3mt transcripts in tissues from juveniles and adults, and RT-PCR analysis from replicate adult animals demonstrated constitutive expression of As3mt in branchial sac, gastrointestinal tract, and heart. 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 intestinaJis 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.

Purpose/Objective:

These ms describes annotation of the arsenic (+3 0xidation state) methyltransferase (As3mt) gene in the sea squirt Ciona intestinalis. The arsenic methylation phenotype is also determined in this species. This research demonstrates the near universality of As3mt in deuterostomes and suggests that Ciona could be used as a model organism in the study of arsenic metabolisim and toxicity. -

URLs/Downloads:

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Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Start Date: 01/01/2010
Completion Date: 01/01/2010
Record Last Revised: 09/02/2010
Record Created: 07/29/2009
Record Released: 07/29/2009
OMB Category: Other
Record ID: 212142

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB

INTEGRATED SYSTEMS TOXICOLOGY DIVISION

PHARMACOKINETICS BRANCH