The effect of brevenal on brevetoxin-induced DNA damage in human lymphocytes

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Daniel G. Baden (Creator)

Andrea J. Bourdelais (Creator)

James E. Gibson (Creator)

Qing Hu (Creator)

Andrew Sayer (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Brevenal is a nontoxic short-chain trans-syn polyether that competes with brevetoxin (PbTx) for the active site on voltage-sensitive sodium channels. The PbTxs are highly potent polyether toxins produced during blooms of several species of marine dinoflagellates most notably Karenia brevis. Blooms of K. brevis have been associated with massive fish kills marine mammal poisoning and are potentially responsible for adverse human health effects such as respiratory irritation and airway constriction in beach-goers. Additionally the consumption of shellfish contaminated with PbTxs results in neurotoxic shellfish poisoning (NSP). The purpose of the present study was to determine whether PbTx could induce DNA damage in a human cell type the lymphocyte and if so whether the damage could be antagonized or ameliorated by brevenal a brevetoxin antagonist. The DNA damage may occur through both endogenous and exogenous physiological and pathophysiological processes. Unrepaired or erroneously repaired DNA damage may result in gene mutation hromosome aberration and modulation of gene regulation which have been associated with immunotoxicity and carcinogenesis. A single-cell gel electrophoresis assay or comet assay was used o determine and compare DNA damage following various treatments. The data were expressed as tail moments which is the percentage of DNA in the tail multiplied by the length between the center of the head and center of the tail (in arbitrary units). The negative control tail moment was 29.2 (SE=±0.9) whereas the positive control (hydrogen peroxide) was 72.1 (1.5) and solvent (ethanol) was 24.2 (2.1). The PbTx-2 (from Sigma St. Louis MO USA) 10−8 M was 41.3 (3.6) PbTx-9 (Sigma) 10−8 M was 57.0 (5.3) PbTx-2 (from University of North Carolina at Wilmington UNCW) 10−8 M was 49.4 (9.9) and PbTx-3 (UNCW) 10−8 M was 64.0 (6.4). 1.0 μg/ml brevenal applied 1 h before the PbTxs protected the lymphocytes from DNA damage; PbTx-2 (Sigma) 31.3 (2.1); PbTx-9 (Sigma) 35.5 (2.9); PbTx-2 (UNCW) 33.9 (1.4); PbTx-3 (UNCW) 34.9 (1.25). The tail moment for 1.0 μg/ml brevenal alone was 30.8 (2.6). The results indicate that extensive genotoxic damage is induced by PbTx-2 and 9 (Sigma) and PbTx-2 and 3 (UNCW) in normal human lymphocytes which is fully antagonized by brevenal. This suggests that the immune systems of individuals exposed to PbTx during harmful algal bloom (HAB) events may be at risk. Originally published Archives in Toxicology Vol. 79 No. 11 Nov 2005

Additional Information

Publication

Other

Archives of Toxicology. 79:11(November 2005) p. 683-688.

Language: English

Date: 2011

Keywords

brevetoxin, brevenal, lymphocytes, gel electrophoresis, tail moment

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