Mutagenic And Genotoxic Activities Of Phospholipase A2 Bothropstoxin-I From Bothrops Jararacussu In Drosophila Melanogaster And Human Cell Lines

Phospholipase A(2) Bothropstoxin-I (PLA(2) BthTX-I) is a myotoxic Lys49-PLA(2) from Bothrops jararacussu snake venom. In order to evaluate the DNA damage caused by BthTX-I, we used the Somatic Mutation and Recombina-tion 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 mu g/mL) were used and no significant changes in the survival rate were ob-served. 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 mu g/mL highly mutagenic and 107.5 mu g/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 mu g/mL) induced decrease in HUVEC cell viability, as well as in DU-145 cells at concentrations of 10, 25, and 50 mu g/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 PLA(2) BthTX-I and its possible use in therapeutic strategies against cancer. (C) 2021 Elsevier B.V. All rights reserved.