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首页> 外文期刊>Archives of Toxicology >The effect of brevenal on brevetoxin-induced DNA damage in human lymphocytes.
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The effect of brevenal on brevetoxin-induced DNA damage in human lymphocytes.

机译：brevenal对短杆菌毒素诱导的人类淋巴细胞DNA损伤的影响。

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摘要

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, chromosome 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 to 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 mug/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 mug/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.
机译：Brevenal是一种无毒的短链反式聚醚，可与短毒素（PbTx）竞争电压敏感钠通道上的活性位点。 PbTx是在几种海洋鞭毛鞭毛藻繁殖过程中产生的强效聚醚毒素。短毛K.布鲁姆氏菌的开花与大量鱼类死亡，海洋哺乳动物中毒有关，并可能对人类健康造成不利影响，例如泳客呼吸道刺激和气道收缩。此外，食用被PbTxs污染的贝类会导致神经毒性贝类中毒（NSP）。本研究的目的是确定PbTx是否能在人类细胞类型（淋巴细胞）中诱导DNA损伤，如果是，则可以通过短毒素毒素brevenal拮抗或减轻损伤。 DNA损伤可能通过内源性和外源性生理和病理生理过程发生。未经修复或错误修复的DNA损伤可能导致基因突变，染色体畸变和基因调控调节，这些都与免疫毒性和致癌作用有关。单细胞凝胶电泳测定法或彗星测定法用于确定和比较各种处理后的DNA损伤。数据以尾矩表示，尾矩是尾巴中DNA的百分比乘以头部中心和尾巴中心之间的长度（以任意单位表示）。阴性对照尾矩为29.2（SE = + /-0.9），而阳性对照（过氧化氢）为72.1（1.5），溶剂（乙醇）为24.2（2.1）。 PbTx-2（来自美国密苏里州圣路易斯的西格玛）的10（-8）M为41.3（3.6），PbTx-9（西格玛）的10（-8）M为57.0（5.3），PbTx- 2（来自北卡罗来纳大学威尔明顿分校，UNCW），10（-8）M为49.4（9.9），PbTx-3（UNCW），10（-8）M为64.0（6.4）。在PbTxs保护淋巴细胞免受DNA损伤之前1小时施用1.0杯/毫升的布氏剂。 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）。仅1.0杯/毫升布氏针的尾部弯矩为30.8（2.6）。结果表明，正常人淋巴细胞中，PbTx-2和9（Sigma）以及PbTx-2和3（UNCW）引起了广泛的遗传毒性损害，而被brevenal完全拮抗。这表明在有害藻华（HAB）事件期间暴露于PbTx的个体的免疫系统可能处于危险之中。

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