Mutagenic and genotoxic activities of Phospholipase A 2 Bothropstoxin-I from Bothrops jararacussu in Drosophila melanogaster and human cell lines.

Autor: Naves MPC; Institute of Biotechnology, Federal University of Uberlândia, Campus Umuarama, Uberlândia, MG, Brazil., de Morais CR; Institute of Biotechnology, Federal University of Uberlândia, Campus Umuarama, Uberlândia, MG, Brazil., de Freitas V; Institute of Biotechnology, Federal University of Uberlândia, Campus Umuarama, Uberlândia, MG, Brazil., Ribeiro DL; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil., Lopes DS; Multidisciplinary Institute in Health, Federal University of Bahia, Vitória da Conquista, BA, Brazil., Antunes LMG; Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., de Melo Rodrigues V; Institute of Biotechnology, Federal University of Uberlândia, Campus Umuarama, Uberlândia, MG, Brazil., de Rezende AAA; Institute of Exact and Natural Sciences of Pontal, Federal University of Uberlândia, Campus Pontal, Ituiutaba, MG, Brazil., Spanó MA; Institute of Biotechnology, Federal University of Uberlândia, Campus Umuarama, Uberlândia, MG, Brazil. Electronic address: maspano@ufu.br.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2021 Jul 01; Vol. 182, pp. 1602-1610. Date of Electronic Publication: 2021 May 24.
DOI: 10.1016/j.ijbiomac.2021.05.114
Abstrakt: 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 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 PLA 2 BthTX-I and its possible use in therapeutic strategies against cancer.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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