Monster Seminar JAM - DNA Microarrays and their Application to the Toxicology of the Harmful Algal Bloom Toxin Azaspiracid
Dr. Mike Twiner, Center for Coastal Environmental Health and Biomolecular Research at Charleston (CCEHBR), NOAA/NOS/NCCOS
Azaspiracid (AZA) is a newly identified phycotoxin reported to accumulate in shellfish and cause severe human intoxications in several European countries. AZA may also be a concern for North American shellfish managers as it was just recently found in mussels grown off the coast of Eastern Canada. To date, very little is known about the ecological or biochemical effects of this toxin. Our investigations have shown that the potential ecological health effects of AZA can be demonstrated by microinjection of AZA-1 into developing medaka (Oryzias latipes) fish eggs. In a dose-dependent manner, AZA caused developmental retardation, bradycardia, reduced hatching success, and reduced viability, collectively illustrating the teratogenicity of this toxin (Colman et al, 2005). Upon further examination with several mammalian cell types and based on published mouse bioassay reports, the highly and broadly toxic nature of AZA was shown by the low nanomolar EC50 cytotoxicity values, making AZA one of the most cytotoxic phycotoxins known (Twiner et al., 2005). When human lymphocyte T cells, used as a model cell type, are exposed to AZA, they undergo a dramatic rearrangement of their peripheral F-actin cytoskeleton resulting in rapid functional inability. Such a loss of cell function in an important immune cell type may account for the immunological effects of AZA observed in vivo during low dose exposures. Whole genome DNA microarrays that assessed gene expression patterns during AZA exposure have identified very specific hypothesis-based research questions. Subsequently, specific biochemical pathways of interest have been identified that appear to be instrumental in eliciting the toxic nature of AZA (Twiner et al, submitted). These pathways of interest are being further validated using in vivo models.
Seattle Yacht Club
1807 East Hamlin Street
Date and Time:
November 9, 2006,
11:00 am - 12:30 pm