Mutagenic and genotoxic activities of Phospholipase A2 Bothropstoxin-I from Bothrops jararacussu in Drosophila melanogaster and human cell lines

• Published in: International journal of biological macromolecules 2021-07, Vol.182, p.1602-1610
• Main Authors: Naves, Maria Paula Carvalho, de Morais, Cássio Resende, de Freitas, Vitor, Ribeiro, Diego Luis, Lopes, Daiana Silva, Antunes, Lusânia Maria Greggi, de Melo Rodrigues, Veridiana, de Rezende, Alexandre Azenha Alves, Spanó, Mário Antônio
• Format: Article
• Language: English
• Subjects: Comet assay; Lys49-PLA2; Myotoxin; SMART; Somatic mutation and recombination test
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2021.05.114

Phospholipase A2 Bothropstoxin-I (PLA2 BthTX-I) is a myotoxic Lys49-PLA2 from Bothrops jararacussu snake venom. In order to evaluate the DNA damage caused by BthTX-I, we used the Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster and Comet assay in HUVEC and DU-145 cells. For SMART, different concentrations of BthTX-I (6.72 to 430 μg/mL) were used and no significant changes in the survival rate were observed. Significant frequency of mutant spots was observed for the ST cross at the highest concentration of BthTX-I due to recombinogenic activity. In the HB cross, BthTX-I increased the number of mutant spots at intermediate concentrations, being 53.75 μg/mL highly mutagenic and 107.5 μg/mL predominantly recombinogenic. The highest concentrations were neither mutagenic nor recombinogenic, which could indicate cytotoxicity in the wing cells of D. melanogaster. In vitro, all BthTX-I concentrations (1 to 50 μg/mL) induced decrease in HUVEC cell viability, as well as in DU-145 cells at concentrations of 10, 25, and 50 μg/mL. The comet assay showed that in HUVEC and DU-145 cells, all BthTX-I concentrations promoted increase of DNA damage. Further studies should be performed to elucidate the mechanism of action of PLA2 BthTX-I and its possible use in therapeutic strategies against cancer. •BthTX-I did not change the survival rate of D. melanogaster.•BthTX-I was recombinogenic at the highest concentration (ST cross).•BthTX-I was mutagenic/recombinogenic at intermediate concentrations (HB cross).•BthTx-I promoted the decrease in HUVEC and DU-145 cell viability.•BthTx-I was genotoxic to HUVEC and DU-145 cells, in vitro.