Melegari Silvia P, de Carvalho Pinto Cátia R S, Moukha Serge, Creppy Edmond E, Matias William G
a Department of Sanitary and Environmental Engineering , Federal University of Santa Catarina, Campus Universitário , Florianópolis , Santa Catarina , Brazil.
b UFR des Sciences Pharmaceutiques , Université Victor Segalen Bordeaux , Bordeaux Cedex , France.
J Toxicol Environ Health A. 2015;78(19):1189-200. doi: 10.1080/15287394.2015.1072069. Epub 2015 Oct 5.
Since the cyanotoxin saxitoxin (STX) is a neurotoxin and induces ecological changes in aquatic environments, a potential risk to public and environmental health exists. However, data on STX-mediated cytotoxic and genotoxic effects are still scare. In order to gain a better understanding of the effects of this toxin, the cytotoxic and genotoxic potential of STX was examined in two mammalian cell lines. Neuro 2A (N2A), a neuroblastoma mouse cell line, and Vero cell line, derived from Vero green monkey kidney cells, were exposed to several concentrations of STX ranging from 0.5 to 64 nM to determine cell viability, induction of apoptosis (DNA fragmentation assay), and formation of micronuclei (MN) (cytokinesis-block micronucleus assay; CBMN) following 24 h of incubation. The half maximal effective concentration (EC50) values for STX calculated in cell viability tests were 1.01 nM for N2A and 0.82 nM for Vero cells. With increasing STX concentration there was evidence of DNA fragmentation indicating apoptosis induction in Vero cells with a 50% increase in DNA fragmentation compared to control at the highest STX concentration tested (3 nM). The results demonstrated no significant changes in the frequency of micronucleated binucleated cells in N2A and Vero cells exposed to STX, indicating the absence of genotoxicity under these test conditions. There was no apparent cellular necrosis as evidenced by a lack of formation of multinucleated cells. In conclusion, data reported herein demonstrate that STX produced death of both cell types tested through an apoptotic process.
由于蓝藻毒素石房蛤毒素（STX）是一种神经毒素，会在水生环境中引发生态变化，因此对公众健康和环境健康存在潜在风险。然而，关于STX介导的细胞毒性和基因毒性作用的数据仍然匮乏。为了更好地了解这种毒素的作用，我们在两种哺乳动物细胞系中检测了STX的细胞毒性和基因毒性潜力。将源自小鼠神经母细胞瘤细胞系的Neuro 2A（N2A）和源自非洲绿猴肾细胞的Vero细胞系暴露于0.5至64 nM的几种浓度的STX中，孵育24小时后，测定细胞活力、凋亡诱导（DNA片段化检测）和微核形成（细胞分裂阻滞微核检测；CBMN）。在细胞活力测试中计算出的STX的半数最大有效浓度（EC50）值，N2A细胞为1.01 nM，Vero细胞为0.82 nM。随着STX浓度的增加，有证据表明Vero细胞中出现DNA片段化，表明诱导了凋亡，在测试的最高STX浓度（3 nM）下，与对照相比，DNA片段化增加了50%。结果表明，暴露于STX的N2A和Vero细胞中微核双核细胞的频率没有显著变化，表明在这些测试条件下不存在基因毒性。没有明显的细胞坏死，多核细胞的形成缺乏证明了这一点。总之，本文报道的数据表明，STX通过凋亡过程导致了所测试的两种细胞类型的死亡。
