期刊
TOXICON
卷 45, 期 7, 页码 891-900出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.toxicon.2005.02.015
关键词
azaspiracids; lymphocyte; shellfish; phycotoxins; cytotoxicity
Azaspiracid-1 (AZA-1) is a newly identified phycotoxin reported to accumulate in molluscs from several northern European countries and documented to have caused severe human intoxications. The mechanism of action of AZA-1 is unknown. Our initial investigations have shown that AZA-1 is cytotoxic to a range of cell types. Cytotoxicity was evident in all seven cell types tested, suggesting a broad-spectrum mode of action, and was both time- and concentration-dependent. However, AZA-1 took an unusually long time ( > 24 h) to cause complete cytotoxicity in most cell types, with the exception of the rat pituitary GH(4)C(1). Extended exposure times did not always lower the EC50 value for a given cell line, but always resulted in more complete cytotoxicity over a very narrow concentration range. The Jurkat cell line (human lymphocyte T) appeared to be very sensitive to AZA-1, although the EC50 values (24-72 h) for all the cell types were in the low nanomolar range (0.9-16.8 nM). The effect of AZA-1 on membrane integrity was tested on Jurkat cells and these data confirm our visual observations of cytotoxicity and necrotic cell lysis following exposure of Jurkat cells to AZA-1 and suggest that AZA-1 has some properties unique among marine algal toxins. Additionally, there were dramatic effects of AZA-1 on the arrangement of F-actin with the concurrent loss of pseudopodia, cytoplasmic extensions that function in mobility and chemotaxis. Although these phycotoxinspecific effects of AZA-1 suggest a possible site of action, further work using cell-based approaches is needed to determine the precise mode of action of AZA-1. (c) 2005 Elsevier Ltd. All rights reserved.
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