In vitro and in silico assessment of cytotoxicity and chromosome instability induced by saxitoxin in human derived neural cell line

被引:5
作者
Constante, Juliany S. [1 ]
Al Khateeb, Juliana E. [1 ]
De Souza, Ana Paula [1 ]
Conter, Felipe U. [2 ]
Lehmann, Mauricio [1 ]
Yunes, Joao S. [3 ]
Dihl, Rafael R. [1 ,4 ]
机构
[1] Univ Luterana Brasil ULBRA, Programa Posgrad Biol Celular & Mol Aplicada Saud, Lab Anal Toxicogenet Celular, Av Farroupilha,8001,Predio 22,4 Andar, BR-92425900 Canoas, RS, Brazil
[2] Univ Luterana Brasil ULBRA, Programa Posgrad Biol Celular & Mol Aplicada Saud, Lab Biol Canc, Av Farroupilha,8001,Predio 22,5 Andar, BR-92425900 Canoas, RS, Brazil
[3] Univ Fed Rio Grande FURG, Inst Oceanog, Lab Cianobacterias & Ficotoxinas, Av Italia,Km 8, BR-96203900 Rio Grande, RS, Brazil
[4] Univ Luterana Brasil ULBRA, Programa Posgrad Odontol, Av Farroupilha 8001, BR-92425900 Canoas, RS, Brazil
来源
ANAIS DA ACADEMIA BRASILEIRA DE CIENCIAS | 2022年 / 94卷
关键词
STX; micronucleus; cytostasis; apoptosis; systems biology; PARALYTIC SHELLFISH TOXINS; OXIDATIVE STRESS; NETWORKS; TISSUE;
D O I
10.1590/0001-3765202220220029
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
In freshwater, saxitoxins (STX) are produced by different cyanobacteria genera, including Raphidiopsis. Data regarding cytogenotoxicity effects of STX on human cells are scarse, this merit further studies of its toxicology. This study assessed the cytotoxicity and the chromosome instability of STX on SHSY-5Y human cell line. The CBMN assay allows the detection of chromosome breaks and abnormal chromosomal segregation. Additionally, in silico systems biology approach, used to search for known and predicted interaction networks, was applied to study the interactions between STX and SHSY-5Y cellular components. The results of the CBMN assay demonstrated that STX concentrations of 2.5 - 10 mu g/L induced cytostasis and chromosome instability in a dose-response relationship. Apoptosis was detected after exposure of SHSY5Y cultured cells to STX concentration of 10 mu g/L. The results of the systems biology analysis revealed the interaction of STX with proteins related with acetylcoline pathway, cell cycle regulation and apoptosis. Furthermore, combining the in vitro and in silico approachs, it was possible to suggest a mechanism of action of STX in SHSY-5Y cells. Overall, the data demonstrated the cytotoxicity and mutagenicity of environmentally relevant concentrations of STX. These results should be considered when setting up guidelines for monitoring STX in water supply.
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页数:13
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