RESUMO
Pesticides use increased worldwide with a record in Brazil. Although several works addressed the effects of pesticides on living organisms, only a few considered their mixture, and even fewer tried to unravel their role in tumoral progression. Due to the relevance of cancer, in the present study, the effects of the mixture of pesticides widely used in Brazil (Glyphosate, 2,4-dichlorophenoxyacetic acid, Mancozeb, Atrazine, Acephate, and Paraquat) and their main metabolites (Aminomethylphosphonic Acid, 2,4-diclorophenol, Ethylenethiourea, Desethylatrazine, Methamidophos, and Paraquat) were investigated on the malignancy phenotype of murine melanoma B16-F1 cells after acute (24 h) and chronic (15 days) exposures. The tested concentrations were based on the Acceptable Daily Intake (ADI) value established by Brazilian legislation. The set of results showed that these chemicals modulate important parameters of tumor progression, affecting the expression of genes related to tumor aggressiveness (Mmp14 and Cd44) and multidrug resistance (Abcb1, Abcc1, and Abcc4), as well as tissue inhibitors of metalloproteinases (Timp1, Timp2, and Timp3). These findings revealed an absence of cytotoxicity but showed modulation of migration, invasion, and colonization capacity of B16-F1 cells. Together, the results point to some negative ways that exposure to pesticides can affect the progression of melanoma and raise a concern related to the increasing trend in pesticide use in Brazil, as the country is one of the major world food suppliers.
Assuntos
Melanoma , Praguicidas , Animais , Camundongos , Praguicidas/toxicidade , Paraquat , Fenótipo , Misturas ComplexasRESUMO
A promising use of bismuth nanoparticles (BiNPs) for different biomedical applications leads to a search for the elucidation of their toxicity mechanisms, since toxicity studies are still at early stage. In the current study, cytotoxic effects of BiNPs produced by laser ablation in solution (LASiS) was investigated in the murine macrophage line RAW 264.7. The cells were exposed to 0.01-50 µg ml-1 of BiNPs for 24 and 48 h and then cytotoxicity assays were performed. Decrease of MTT conversion to formazan and of cell attachment were observed with no effects on cell proliferation. No loss of membrane integrity or significant changes of ROS and RNS levels were observed in exposed cells. Foremost, increased phagocytic activity and DNA repair foci occurred for cells exposed to BiNPs. These effects are important findings that must be considered in the case of biomedical application of BiNPs, since inappropriate macrophages activation and inactivation may lead to immunotoxicity. Bismuth nanoparticles (BiNPs) produced by laser ablation in solution and stabilized with BSA decrease enzyme-dependent MTT conversion to formazan and increase phagocytic activity and DNA repair foci in murine macrophage line RAW 264.7 when exposed to 50 µg ml-1. These effects are findings that should be considered in the case of biomedical application of BiNPs, since inappropriate macrophages activation and inactivation may lead to immunotoxicity.
Assuntos
Bismuto/toxicidade , Formazans/química , Macrófagos/efeitos dos fármacos , Nanopartículas Metálicas/química , Células RAW 264.7/efeitos dos fármacos , Animais , Bismuto/química , Adesão Celular , Ciclo Celular , Proliferação de Células , Sobrevivência Celular , DNA/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Reparo do DNA , Lasers , Macrófagos/citologia , Camundongos , Fagocitose , Células RAW 264.7/citologia , Espécies Reativas de Oxigênio , Sais de Tetrazólio/química , Tiazóis/químicaRESUMO
Gold (AuNP) and silver (AgNP) nanoparticles have been incorporated into many therapeutic and diagnostic applications. However, previous studies revealed toxic properties as well as the hormesis phenomenon of many nanoparticles in different biological models. To evaluate the effects of low concentrations of AuNP and AgNP on murine melanoma cells B16F1 and B16F10 and relate them with phenotype changes, cells were exposed for 24 and 48 h. No cytotoxicity was observed for B16 cells through neutral red, MTT, trypan blue, and crystal violet assays at concentrations from 0.01 to 10 ng mL-1. Likewise, the nanoparticles did not interfere with drug-efflux activity, cell migration, cell cycle, and colony formation. Slight toxicity was observed for B16F10 exposed to 100 ng mL-1, with a decreased number of viable and attached cells, indicating differential sensitivity of B16F1 and B16F10 cells to the nanoparticles. Furthermore, colony size dispersion decreased for both B16 cell sub-lines. Therefore, there is no evidence that the tested concentrations of AuNP and AgNP can render B16 cells more aggressive and malignant, which is important since both nanoparticles are already largely used in nanotechnological products. Considering studies that have showed the hormesis effect of nanoparticles at low concentrations, which could protect cancer cells against chemotherapy, further investigation is advised.