title: Evaluation of Cytotoxicity and Cell Death Induced In Vitro by Saxitoxin in Mammalian Cells.
abstract: 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.
authors.affiliation: a Department of Sanitary and Environmental Engineering , Federal University of Santa Catarina, Campus Universitário , Florianópolis , Santa Catarina , Brazil.
authors.forename: Silvia P
authors.initials: SP
authors.lastname: Melegari
authors.affiliation: a Department of Sanitary and Environmental Engineering , Federal University of Santa Catarina, Campus Universitário , Florianópolis , Santa Catarina , Brazil.
authors.forename: Cátia R S
authors.initials: CR
authors.lastname: de Carvalho Pinto
authors.affiliation: b UFR des Sciences Pharmaceutiques , Université Victor Segalen Bordeaux , Bordeaux Cedex , France.|c INRA-Centre de Recherche de Bordeaux Aquitaine , Unité de Mycologie et de Sécurité des Aliments, Villenave d'Ornon Cedex , France.
authors.forename: Serge
authors.initials: S
authors.lastname: Moukha
authors.affiliation: b UFR des Sciences Pharmaceutiques , Université Victor Segalen Bordeaux , Bordeaux Cedex , France.
authors.forename: Edmond E
authors.initials: EE
authors.lastname: Creppy
authors.affiliation: a Department of Sanitary and Environmental Engineering , Federal University of Santa Catarina, Campus Universitário , Florianópolis , Santa Catarina , Brazil.
authors.forename: William G
authors.initials: WG
authors.lastname: Matias
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D066298:In Vitro Techniques; D051379:Mice; D015162:Micronucleus Tests; D012530:Saxitoxin / Q000633:toxicity*; D014709:Vero Cells / Q000187:drug effects
chemical_list: D012530:Saxitoxin