Toxicology Unit, Department of Psychobiology, University of A Coruña, A Coruña, Spain.
J Toxicol Environ Health A. 2011;74(15-16):980-92. doi: 10.1080/15287394.2011.582026.
Marine algal blooms have become a public health concern due to increasing frequency in the environment and severity of exposure consequences. Human intoxications produced by phycotoxins occur globally through consumption of marine fish products containing bioaccumulated toxins. Okadaic acid (OA) is the main representative of diarrheic shellfish poisoning (DSP) toxin. OA was found to inhibit protein phosphatases and to produce oxidative damage, as well as to disturb different cellular functions including cell cycle, gene expression, and DNA repair mechanisms. The aim of this study was to determine whether OA induced genotoxicity by using a micronucleus (MN) test and γH2AX analysis, and to elucidate the underlying mechanisms. Human peripheral blood leukocytes, neuroblastoma cells (SHSY5Y), and hepatoma cells (HepG2) were treated with a range of OA concentrations in the presence and absence of S9 fraction. MN induction was observed in leukocytes at all concentrations tested, and in SHSY5Y and HepG2 cells only at the highest concentration (1000 nM). In contrast, γH2AX analysis was only positive for HepG2 cells. Taking together these data, in addition to the comet assay results obtained in a previous study in this issue, OA was found to exert a either a clastogenic or aneugenic effect dependent upon the cell types examined.
由于海洋藻类大量繁殖在环境中越来越频繁,暴露后果也越来越严重,因此引起了公众健康方面的关注。人类因食用含有生物累积毒素的海洋鱼类产品而受到藻类毒素中毒,这种情况在全球范围内时有发生。冈田酸(OA)是腹泻性贝类毒素(DSP)毒素的主要代表。研究发现,OA 能够抑制蛋白磷酸酶,产生氧化损伤,并扰乱包括细胞周期、基因表达和 DNA 修复机制在内的多种细胞功能。本研究旨在通过微核(MN)试验和γH2AX 分析来确定 OA 是否会诱导遗传毒性,并阐明其潜在机制。用一系列 OA 浓度在有或无 S9 部分的情况下处理人外周血白细胞、神经母细胞瘤细胞(SHSY5Y)和肝癌细胞(HepG2)。在所有测试浓度下均观察到白细胞中的 MN 诱导,而在 SHSY5Y 和 HepG2 细胞中仅在最高浓度(1000 nM)下观察到。相反,γH2AX 分析仅对 HepG2 细胞呈阳性。综合这些数据,再加上之前在本问题的另一项研究中获得的彗星试验结果,发现 OA 根据所检查的细胞类型表现出致裂或致畸效应。