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Title: Comparative effects of the marine algal toxins azaspiracid-1, -2, and -3 on Jurkat T lymphocyte cells
Authors: Twiner, M.
El-Ladki, R.
Kilcoyne, J.
Doucette, G.J.
Keywords: azaspiracid (AZA)
structure-activity relationship
T lymphocytes
toxic equivalence factor (TEF)
Issue Date: 2012
Publisher: ACS Publications
Citation: Twiner, M. J., El-Ladki, R., Kilcoyne, J., & Doucette, G. J. (2012). Comparative Effects of the Marine Algal Toxins Azaspiracid-1, -2, and -3 on Jurkat T Lymphocyte Cells. Chemical Research in Toxicology, 25(3), 747–754. doi:10.1021/tx200553p
Series/Report no.: Chem. Res. Toxicol.;25 (3), pp 747–754
Abstract: Azaspiracids (AZA) are polyether marine toxins of dinoflagellate origin that accumulate in shellfish and represent an emerging human health risk. Although monitored and regulated in many European and Asian countries, there are no monitoring programs or regulatory requirements in the United States for this toxin group. This did not prove to be a problem until June 2009 when AZAs were identified in US seafood for the first time resulting in human intoxications and further expanding their global distribution. Efforts are now underway in several laboratories to better define the effects and mechanism(s) of action for the AZAs. Our investigations have employed Jurkat T lymphocyte cells as an in vitro model to characterize the toxicological effects of AZA1, AZA2, and AZA3. Cytotoxicity experiments employing a metabolically based dye (i.e., MTS) indicated that AZA1, AZA2, and AZA3 each elicited a lethal response that was both concentration- and time-dependent, with EC50 values in the sub- to low nanomolar range. On the basis of EC50 comparisons, the order of potency was as follows: AZA2 > AZA3 > AZA1, with toxic equivalence factors (TEFs) relative to AZA1 of 8.3-fold and 4.5-fold greater for AZA2 and AZA3, respectively. Image analysis of exposed cells using Nomarski differential interference contrast (DIC) imaging and fluorescent imaging of cellular actin indicated that the morphological effects of AZA1 on this cell type are unique relative to the effects of AZA2 and AZA3. Collectively, our data support the growing body of evidence suggesting that natural analogues of AZA are highly potent and that they may have multiple molecular targets.
Description: Peer-reviewed. This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Chemical Research in Toxicology following peer review. The definitive publisher-authenticated version is available online at:DOI: 10.1021/tx200553p
ISSN: 1520-5010
Appears in Collections:Peer Reviewed Scientific Papers

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