Document Detail

Mussel blood cells, resistant to the cytotoxic effects of okadaic acid, do not express cell membrane p-glycoprotein activity (multixenobiotic resistance).
MedLine Citation:
PMID:  12932699     Owner:  NLM     Status:  MEDLINE    
Okadaic acid (OA) is a dinoflagellate toxin, accumulating in shellfish and causing diarrhetic shellfish poisoning (DSP) in humans. OA is a highly cytotoxic agent in most cell lines because of its inhibiting properties of protein phosphatases. So far, the cytotoxicity of OA in mussels, the main vectors of DSP, has not been investigated. In this paper, the viability of mussel (Mytilus edulis) blood cells incubated in 10 nM-1 microM OA was studied. After 72 h of exposure, viability was reduced to 54% in 1 microM OA compared with 88% in control cells. This yielded a LC50 of >1 microM for OA, which is 30-1000-times higher compared with other cell types. It was hypothesised that P-glycoprotein (p-gp) activity (multixenobiotic resistance, MXR) contributed to the resistance to OA. Vincristine and rhodamine B was used as p-gp substrates and verapamil or staurosporine (ST) as inhibitors of p-gp transport. However, no indications of cell membrane p-gp activity were detected. Instead, experimental observations led to the conclusion that a MXR transport system was present within lysosomal membranes. Various concentrations of OA did not affect the dynamics of vincristine in blood cells. As a positive control for the assay, p-gp activity was measured in mussel gill tissue. The efflux of rhodamine B was reduced by verapamil, which is, considered evidence for cell membrane p-gp activity, thus the accuracy of the method was confirmed. Rhodamine B efflux was also reduced by OA in gill tissue, which suggested that OA is either a competitive substrate or inhibitor of p-gp activity. When the volume of the lysosomal compartment was measured in blood cells pre-exposed to OA, a significant increase was detected compared with control cells. It was proposed that uptake and storage of OA within the lysosomal system might protect mussel blood cells from the cytotoxic effects of this compound.
Susanne Svensson; Anders Särngren; Lars Förlin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Aquatic toxicology (Amsterdam, Netherlands)     Volume:  65     ISSN:  0166-445X     ISO Abbreviation:  Aquat. Toxicol.     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-08-22     Completed Date:  2003-10-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8500246     Medline TA:  Aquat Toxicol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  27-37     Citation Subset:  IM    
Department of Zoology/Zoophysiology, Göteborg University, Box 463, SE-405 30 Göteborg, Sweden.
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MeSH Terms
Analysis of Variance
Biological Assay
Bivalvia / metabolism*
Cell Survival / drug effects
Drug Resistance, Multiple
Hemocytes / cytology,  drug effects,  metabolism*
Lysosomes / metabolism
Okadaic Acid / toxicity*
P-Glycoprotein / biosynthesis*
Reg. No./Substance:
0/P-Glycoprotein; 0/Rhodamines; 0/Xenobiotics; 14899-08-2/rhodamine B; 57-22-7/Vincristine; 78111-17-8/Okadaic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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