The L-amino acid oxidases isolated and characterized from snake venoms (SV-LAAOs) have become important candidates for models in the development of new drugs and biological tools. Studies have demonstrated that SV-LAAOs isolated from different genera of snakes can promote alterations in the metabolism of cancer cells, and induction of apoptosis by activation of multiple pathways. This pharmacological effect can be explained, in part, by the generation of hydrogen peroxide formed during the catalytic cycle of LAAOs. However, data related to the possible genotoxic and mutagenic effects that these venom proteins can cause to human cells are very scarce. The main objective of this project is the identification of the genomic danger that LAAOs from Calloselasma rhodostoma (CR-LAAO), Bothrops jararaca (BjarLAAO-I) and Crotalus durissus terrificus snake venoms can offer to human cells. For this, we will investigate the ability of these enzymes to cause genotoxic and mutagenic damage in human cells (HepG2 and PBMC), using in vitro assays that quantify the damage caused in the DNA and chromosomes of these cells (comet test and micronucleus). Moreover, we will evaluate whether treatment with different concentrations of the SV-LAAOs is able to induce activation of DNA repair mechanisms, by detecting the expression of genes involved in this process. These data will be very important for the direction of our research in pursuit of the development of more effective antitumor drugs or adjuncts in the treatment of different cancers.
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