RESUMO
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.
Assuntos
Bothrops/metabolismo , Venenos de Crotalídeos/toxicidade , Fosfolipases A2/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Drosophila melanogaster , Células Endoteliais da Veia Umbilical Humana , Humanos , Mutação/genéticaRESUMO
Betulinic acid (BA) is a pentacyclic triterpenoid found in several plant species. Urethane (URE) is a known promutagen. Here, we examine the genotoxicity and mutagenicity of BA alone or in combination with URE using the bone marrow micronucleus assay in mice bone marrow cells and the Somatic Mutation and Recombination Test in Drosophila melanogaster. Findings revealed that BA alone was not genotoxic, but reduced the frequency of micronucleus when compared to the positive control. No significant differences were observed in the cytotoxicity. Biochemical analyzes showed no significant differences for liver (AST and ALT) or renal (creatinine and urea) function parameters, indicating the absence of hepatotoxic and nephrotoxic effects. BA alone did not increase the frequency of mutant spots, but reduced the total frequency of mutant spots when co-administered with URE in both ST and HB crosses. In addition, BA reduced the recombinogenic effect of URE at the highest concentrations of both crosses. In conclusion, under experimental conditions, BA has modulatory effects on the genotoxicity induced by URE in mice, as well as in somatic cells of D. melanogaster. We suggest that the modulatory effects of BA may be mainly due to its antioxidant and apoptotic properties.
Assuntos
Drosophila melanogaster/efeitos dos fármacos , Mutagênese/efeitos dos fármacos , Triterpenos/farmacologia , Uretana/toxicidade , Animais , Antimutagênicos/farmacologia , Antioxidantes/farmacologia , Medula Óssea/efeitos dos fármacos , Carcinógenos/farmacologia , Drosophila melanogaster/genética , Feminino , Cabelo/efeitos dos fármacos , Masculino , Camundongos , Testes de Mutagenicidade , Triterpenos Pentacíclicos , Taxa de Sobrevida , Tricomas/efeitos dos fármacos , Triterpenos/química , Asas de Animais/efeitos dos fármacos , Ácido BetulínicoRESUMO
Water pollution and the increase in genotoxic consequences in aquatic environments are well documented indicating the necessity and importance of biomonitoring programs. The objective of the present study was to determine the environmental quality of water resources and genotoxic potential of materials present within water samples obtained from the Perdizes River and the Mumbuca Stream, located in a region of discharge of wastewater treatment effluents using Tradescantia micronucleus assay (Trad - MCN). Water samples were collected from different locations up and downstream of the wastewater treatment plant during rainy season and subsequently submitted to physico-chemical analysis and Trad-MCN bioassay. The spatial distribution of the physico-chemical parameters assessed suggested that discharges of wastewater treatment effluents reduced water quality at all sites examined. Further, exposure to wastewater treatment effluents produced genotoxic effects on tetrads of Tradescantia pallida. These results reinforce the sensitivity of the Trad-MCN bioassay and its potential application in water quality monitoring programs concomitant with physicochemical evaluation.
Assuntos
Resíduos Industriais/efeitos adversos , Testes para Micronúcleos , Tradescantia/efeitos dos fármacos , Águas Residuárias/toxicidade , Poluentes Químicos da Água/toxicidade , Tradescantia/genéticaRESUMO
Antiparasitic substances are chemicals used to control or kill endoparasites and ectoparasites. Based on the premise that Ivermectin (IVM) and Amoxicillin (AMX) are commonly considered in parasitic control in mammals, the present study aimed to evaluate the carcinogenic and genotoxic potential of different concentrations of IVM and AMX through the detection of epithelial tumor test in Drosophila melanogaster. Third-instar larvae descending from the cross between wts/TM3, Sb1 females and mwh/mwh males were treated with different concentrations of IVM (2.9, 5.8, 11.6 and 23.2 x 10-17 mM) or AMX (1.37, 2.74, 5.48 and 10.9 x 10-16mM). The results revealed that IVM increased the frequency of epithelial tumor in D. melanogaster considering all evaluated concentrations, while AMX showed no carcinogenic effect. Furthermore, the Micronucleus (MN) test in Tradescantia pallida was used to evaluate the genotoxic effect of IVM and AMX. T. pallida individuals were exposed for 8 hours at different concentrations of IVM (5.71, 11.42, 22.84 and 45.68 x 10-5mM) or AMX (5.13, 10.26, 20.52 and 41.05 x 10-3mM). Findings showed an increase in the frequency of micronuclei in T. pallida treated with 11.42, 22.84 and 45.68 x 10-5mM of IVM. We conclude that chronic exposure to IVM is directly associated with events resulting from genetic instability (genotoxicity and carcinogenicity). On the other hand, AMX was neither carcinogenic nor genotoxic for D. melanogaster and T. pallida.
Assuntos
Amoxicilina/toxicidade , Antiparasitários/toxicidade , Carcinógenos/toxicidade , Ivermectina/toxicidade , Mutagênicos/toxicidade , Animais , Carcinoma/induzido quimicamente , Dano ao DNA , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/genética , Feminino , Larva/efeitos dos fármacos , Larva/genética , Masculino , Testes de Mutagenicidade , Tradescantia/efeitos dos fármacos , Tradescantia/genéticaRESUMO
The aim of the present study was to appraise the mutagenic and recombinogenic potential of bupropion hydrochloride (BHc) and trazodone hydrochloride (THc). We used standard (ST) and the high bioactivation (HB) crossings from Drosophila melanogaster in the Somatic Mutation and Recombination Test. We treated third-instar larvae from both crossings with different concentrations of BHc and THc (0.9375 to 7.5â¯mg/mL). BHc significantly increased the frequency of mutant spots in both crossings, except for the lowest concentration in the ST crossing. ST had also the mostly recombinogenic result, and in the HB, BHc was highly mutagenic. On the other hand, THc significantly increased the frequency of mutant spots in both the ST and HB crossings at all concentrations. The three initial concentrations were recombinogenic and the highest concentration was mutagenic for the THc. BHc and THc at high concentrations were toxic, even though their mutagenicity was not dose-related. THc significantly increased the frequency of mutant spots when metabolized, probably as a result of the production of 1-(3'-chlorophenyl) piperazine. BHc was essentially recombinogenic and when metabolized, it became mutagenic. THc was recombinogenic in both crossings. Further studies are needed to clarify the action mechanisms from BHc and THc.
Assuntos
Antidepressivos/toxicidade , Bupropiona/toxicidade , Drosophila melanogaster/efeitos dos fármacos , Mutagênicos/toxicidade , Recombinação Genética/efeitos dos fármacos , Trazodona/toxicidade , Animais , Drosophila melanogaster/genética , Feminino , Masculino , Testes de Mutagenicidade , Mutação , Asas de Animais/efeitos dos fármacosRESUMO
Neonicotinoids and phenylpyrazoles are classes of neurotoxic insecticides which are able to bind at different ligand sites of neural receptors, leading to the deregulation of insect neural activity and hence resulting in death. The misuse or indiscriminate use of these chemicals is directly associated with several toxicological effects in biota and at different trophic levels. Based on this premise, the aim of the present study was to evaluate and compare the genotoxic capacity of different concentrations of thiamethoxam (TMX), acetamiprid (ACP), imidacloprid (IMI) and fipronil (FP) through the Micronucleus Test in Tradescantia pallida (Trad-MCN). After acclimatization (24â¯h), T. pallida stems were treated with stablished concentrations of TMX, ACP, IMI and FP for 8â¯h. Then, the stems of the model organism were submitted to a recovery phase (24â¯h). The young inflorescences were harvested and fixed in Carnoy solution and, after 24â¯h, were conserved in ethanol 70% until the analyzes. The obtained anthers were macerated on slides for microscopy, stained with acetic carmine dye and covered with coverslips before analysis by light microscopy. Considering the insecticides, the micronuclei (MN) frequency in plants treated at concentrations of 0.2 and 0.4â¯gâ¯L-1 for TMX, 0.2; 0.4 and 0.8â¯gâ¯L-1 for ACP, 0.1; 0.2; 0.4; 0.8 and 1.6â¯gâ¯L-1 for IMI and 0.2; 0.4; 0.8 and 1.6â¯gâ¯L-1 for FP differed statistically (pâ¯<â¯0.05, Tukey) from the MN frequency of the negative control. All chemicals evaluated revealed genotoxic activity in T. pallida at the highest concentrations.
Assuntos
Inseticidas/toxicidade , Testes para Micronúcleos , Tradescantia/efeitos dos fármacos , Relação Dose-Resposta a Droga , Testes de Mutagenicidade , Neonicotinoides/toxicidade , Nitrocompostos/toxicidade , PirazóisRESUMO
Melipona scutellaris Latreille, 1811 (Hymenoptera, Apidae) is a pollinator of various native and cultivated plants. Because of the expansion of agriculture and the need to ensure pest control, the use of insecticides such as fipronil (FP) has increased. This study aimed to evaluate the effects of sublethal doses of FP insecticide on M. scutellaris at different time intervals (6, 12, and 24â¯h) after exposure, via individually analyzed behavioral biomarkers (locomotor activity, behavioral change) as well as the effect of FP on different brain structures of bees (mushroom bodies, antennal cells, and optic cells), using sub-individual cell biomarkers (heterochromatin dispersion, total nuclear and heterochromatic volume). Forager bees were collected when they were returning to the nest and were exposed to three different concentrations of FP (0.40, 0.040, and 0.0040â¯ng a.i/bee) by topical application. The results revealed a reduction in the mean velocity, lethargy, motor difficulty, paralysis, and hyperexcitation in all groups of bees treated with FP. A modification of the heterochromatic dispersion pattern and changes in the total volume of the nucleus and heterochromatin were also observed in the mushroom bodies (6, 12, and 24â¯h of exposure) and antennal lobes (6 and 12â¯h) of bees exposed to 0.0040â¯ng a.i/bee (LD50/100). FP is toxic to M. scutellaris and impairs the essential functions required for the foraging activity.
Assuntos
Ecotoxicologia/métodos , Inseticidas/efeitos adversos , Animais , Abelhas , BrasilRESUMO
Nanoparticles have been widely used in several sectors and their long-term effect on the body and environment remains unknown. To evaluate the mutagenic, recombinogenic and carcinogenic potential of 11 nm titanium dioxide nanocrystals (TiO2 NCs), the Somatic Mutation and Recombination Test (SMART) and the Test for Detection of Epithelial Tumors Clones (Warts-Wts) were used, both in Drosophila melanogaster. Third-instar larvae (72 + 4 h), obtained in both tests, were treated with different concentrations of TiO2 NCs ranging from 6.25 to 100 mM. Ultrapure water and urethane were used as negative and positive controls, respectively. At ST cross, all concentrations of TiO2 NCs showed a significant increase in the frequencies of mutant spots, demonstrating higher recombination rates. At the HB cross, only the 50 mM concentration showed a negative result. In the Wts Test, all used concentrations were carcinogenic, except for the 100 mM one, which was toxic. No relationship was demonstrated between the used concentrations and the obtained responses. There was no interference of the cytochrome P450 enzyme complex in the induction of mutant spots.
Assuntos
Carcinógenos/toxicidade , Drosophila melanogaster/efeitos dos fármacos , Mutagênicos/toxicidade , Nanopartículas/toxicidade , Titânio/toxicidade , Animais , Drosophila melanogaster/genética , Testes de Mutagenicidade , Mutação/efeitos dos fármacos , Recombinação Genética/efeitos dos fármacosRESUMO
Thiamethoxam (TMX) belongs to a class of neuro-active insecticides referred as neonicotinoids, while actara® (AC) is one of the most popular TMX-based products in Brazil. The aim of this study was to evaluate the mutagenic, recombinogenic and carcinogenic potential of TMX and AC insecticides. The mutagenic and recombinogenic effect of TMX and AC were evaluated in vivo by the Somatic Mutation and Recombination Test (SMART) while carcinogenic effects were evaluated through the Test for Detection of Epithelial Tumor Clones (wts test), both in somatic cells of Drosophila melanogaster. In the SMART, third instar larvae from standard (ST) and high bioactivation (HB) crosses were treated with different concentrations of TMX and AC (2.4; 4.8; 9.7 × 10-4 mM and 1.9 × 10-3 mM). The results revealed mutagenic effects at the highest concentrations tested in the HB cross. In the test for the detection of epithelial tumor, third instar larvae resulting from the cross between wts/TM3, Sb1 virgin females and mwh/mwh males were treated with the same concentrations of TMX and AC used in the SMART. No carcinogenic effect was observed at any of the concentrations tested. In this work, the inhibition of the mechanism of repair by homologous recombination was observed in flies exposed to 9.7 × 10-4 and 1.9 × 10-3 mM of AC. In conclusion, TMX and AC demonstrated to be a promutagen in the highest concentrations tested.
Assuntos
Drosophila melanogaster/efeitos dos fármacos , Neonicotinoides/farmacologia , Nitrocompostos/farmacologia , Oxazinas/farmacologia , Tiazóis/farmacologia , Animais , Brasil , Carcinogênese/efeitos dos fármacos , Drosophila melanogaster/citologia , Feminino , Inseticidas/farmacologia , Masculino , Mutagênese/efeitos dos fármacos , Testes de Mutagenicidade/métodos , Recombinação Genética/efeitos dos fármacos , TiametoxamRESUMO
Fipronil (FP) is an insecticide that belongs to the phenylpyrazole chemical family and is used to control pests by blocking GABA receptor at the entrance channel of the chlorine neurons. The aim of this study was to evaluate the mutagenic, recombinogenic and carcinogenic potential of FP. The mutagenic and recombinogenic effects were evaluated using the somatic mutation and recombination test (SMART) on wing cells of Drosophila melanogaster. Third instar larvae from standard (ST) and high bioactivation (HB) crosses were treated with different concentrations of FP (0.3, 0.7, 1.5 or 3.0 × 10-5 mM). The results showed mutagenic effects at all concentrations tested in the HB cross; and all concentrations tested in the ST cross, except at concentration of 0.7 × 10-5 mM. The carcinogenic effect of FP was assayed through the test for detection of epithelial tumor (warts) in D. melanogaster. Third instar larvae from wts/TM3 virgin females mated to mwh/mwh males were treated with different concentrations of FP (0.3, 0.7, 1.5 or 3.0 × 10-5 mM). All these concentrations induced a statistically significant increase in tumor frequency. In conclusion, FP proved to be mutagenic, recombinogenic and carcinogenic in somatic cells of D. melanogaster.