RESUMO
Agaricus blazei Murrill, a native mushroom in Brazil, has been widely consumed in different parts of the world due to its medicinal power. Its anticarcinogenic activity has been shown in experimental animals, and antimutagenic activity has been demonstrated only in Salmonella. In this work, the mutagenic and antimutagenic activities of mushroom teas of strains AB96/07, AB96/09 and AB97/11 were evaluated in Chinese hamster V79 cells, using the comet assay and the micronucleus test. The cells were treated with three different concentrations (0.05, 0.1 and 0.15) of teas prepared from a 2.5% aqueous solution, under three different temperatures: (1) room (20-25 degrees C); (2) ice-cold (2-8 degrees C); and (3) warm (60 degrees C). The teas were applied in co-, pre- and post-treatments in combination with the mutagen methyl methanesulfonate (MMS; 1.6x10(-4) and 4x10(-4)M). The duration of the treatment was 1h in the comet assay and 2h in the micronucleus test. The results showed that the mushroom was not mutagenic itself. Nevertheless, the mushroom is an efficient antimutagen against the induction of micronuclei by MMS in all concentrations and preparations tested. The observed reductions in the frequencies of micronuclei ranged from 61.5 (room temperature 0.1% tea in post-treatment) to 110.3% (co-treatment with warm and ice-cold 0.15% tea). In the comet assay, the antimutagenic activity was detected only when the cells were pre-treated with the following teas: warm 0.1 and 0.15%, room temperature 0.05% and ice-cold 0.1%. The results indicate that the mushroom A. blazei extracts are antimutagenic when tested in V79 cells.
Assuntos
Agaricus/química , Antimutagênicos/farmacologia , Dano ao DNA/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Ensaio Cometa , Cricetinae , Cricetulus , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Metanossulfonato de Metila/toxicidade , Testes para Micronúcleos , Mutagênicos/toxicidade , Células Tumorais CultivadasRESUMO
Agaricus blazei Murrill extracts have previously been shown to have anticarcinogenic and antimutagenic properties. These results suggest that antimutagenic activity, besides the modulation of the immune system, might be involved in the anticarcinogenic action of A. blazei. To investigate the possible antimutagenic effect of A. blazei in vivo, we evaluated its effect on clastogenicity induced by cyclophosphamide (CP) in mice, using the micronucleus test in bone marrow (MNPCE) and in peripheral blood (MNRET). Male Swiss mice were treated with CP (25 or 50mg/kg i.p.) or with CP plus mushroom solution at three different temperatures: 4, 21, and 60 degrees C. Aqueous solution of a mixture from various lineages of the mushroom inhibited induction of micronuclei by CP in bone marrow and in peripheral blood of mice. In contrast to the mixture of lineages, a single isolated lineage did not lead to a reduction of CP-induced MN frequencies in either bone marrow or blood cells of mice. The results suggest that under certain circumstances these mushrooms exhibit antimutagenic activities that might contribute to an anticarcinogenic effect.
Assuntos
Agaricus/química , Antimutagênicos/farmacologia , Dano ao DNA/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/patologia , Ciclofosfamida/toxicidade , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Camundongos , Testes para Micronúcleos , Mutagênicos/toxicidade , Reticulócitos/efeitos dos fármacos , Reticulócitos/patologiaRESUMO
We evaluated the antimutagenic effect of Letinula edodes (Berk.) Pegler (Shiitake) on the frequency of micronuclei in mice treated with N-ethyl-N-nitrosourea (ENU) or cyclophosphamide (CP). Mice were orally (gavage) pretreated for 15 consecutive days with solutions of Shiitake (0.6 ml per day, gavage) prepared at three different temperatures: 4, 21 (RT), and 60 degrees C. Then, the animals were intraperitoneally injected on day 15 with CP (25 or 50mg/kg) or ENU (50 mg/kg) and killed 24 or 48 h after treatment for evaluation of micronucleated polychromatic erythrocytes (MNPCEs) in bone marrow and micronucleated reticulocytes (MNRETs). A mixture of L. edodes lineages (LE 95/016, 96/14, 96/17, 96/22, 96/23, 97/27, and 97/28) significantly decreased the frequencies of MNPCEs and MNRETs induced by CP (25 and 50mg/kg). When a single lineage from the mixture (LE 96/17) was tested we also found a significant reduction in the frequencies of MNPCEs and MNRETs induced by both CP or ENU (50mg/kg). The comet assay was also performed 3h after ENU treatment using mice pretreated with the single lineage (LE 96/17) of L. edodes. The results showed a high degree of variability with some indications of an antigenotoxic effect. Taken together, our data show that solutions from Shiitake inhibit in vivo mutagenicity of CP and ENU.
Assuntos
Antimutagênicos/farmacologia , Dano ao DNA/efeitos dos fármacos , Extratos Vegetais/farmacologia , Cogumelos Shiitake/química , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/patologia , Contagem de Células , Ensaio Cometa , Ciclofosfamida/toxicidade , Eritrócitos/efeitos dos fármacos , Etilnitrosoureia/toxicidade , Masculino , Camundongos , Testes para Micronúcleos , Mutagênicos/toxicidade , Reticulócitos/efeitos dos fármacos , Reticulócitos/patologia , TemperaturaRESUMO
The mutagenic and carcinogenic effects of genotoxic agents on exposed people have constituted an increasing concern. Therefore, the objective of this work was to assess DNA damage in lymphocytes of workers exposed to X-radiation using the cytokinesis-blocked micronucleus test and the comet assay (single-cell gel electrophoresis), and to compare these two techniques in the monitoring of exposed populations. The cytokinesis-blocked micronucleus test and the comet assay were employed in the monitoring of 22 workers occupationally exposed to X-radiation in a hospital in southern Brazil. The frequency of dicentric bridges was also measured. The results of both assays and the frequency of dicentric bridges revealed a significant increase in genetic effects on the cells of exposed individuals. Age was significantly correlated with micronucleus frequency and damage index in the comet assay. The concomitant analysis of dicentric bridges when determining micronucleus frequency does not require much extra work, and may serve as a reference to the type of mutagenic effect (clastogenic or aneugenic). The combination of the alkaline comet assay with the cytokinesis-blocked micronucleus test appears to be very informative for the monitoring of populations chronically exposed to genotoxic agents.
Assuntos
Dano ao DNA/efeitos da radiação , Linfócitos/efeitos da radiação , Exposição Ocupacional , Monitoramento de Radiação/métodos , Raios X , Adulto , Fatores Etários , Ensaio Cometa , Feminino , Humanos , Linfócitos/fisiologia , Masculino , Testes para Micronúcleos , Pessoa de Meia-Idade , FumarRESUMO
The analysis of the genotoxicity of praziquantel, an effective antihelminthic widely used in countries where parasitic infections are still serious public health problems, has been extensively performed using diverse in vitro and in vivo assays and endpoints. However, results are not conclusive, since reports to date indicate either praziquantel is mutagenic, comutagenic, or even antimutagenic. In the present work, the clastogenic potential of praziquantel was investigated in V-79 Chinese hamster fibroblasts and human peripheral blood using a sensitive technique such as the single-cell electrophoresis assay. Results indicate that even though praziquantel induced DNA single-strand breaks both in V-79 cells and unstimulated human leukocytes, this effect was not translated into persistent DNA damage, since neither SCE nor HPRT mutations were induced. This suggests that the effect observed in the SCGE assay is an early event not closely related to praziquantel mutagenicity, because this DNA damage could be efficiently repaired.
Assuntos
Antiplatelmínticos/farmacologia , Células Sanguíneas/efeitos dos fármacos , Dano ao DNA , Eletroforese em Gel de Ágar/métodos , Praziquantel/farmacologia , Adulto , Animais , Células Sanguíneas/química , Linhagem Celular , Cricetinae , Cricetulus , DNA/sangue , DNA/efeitos dos fármacos , Fibroblastos/química , Fibroblastos/efeitos dos fármacos , Humanos , Troca de Cromátide Irmã/efeitos dos fármacosRESUMO
The latex of Christ's Crown (Euphorbia milii var. hislopii, syn. E. splendens var. hislopii) is a highly active plant molluscicide and could be used for snail control to reduce the prevalence of schistosomiasis in endemic areas. In the course of its toxicological evaluation, the mutagenicity of the latex of Euphorbia milii was tested in mammalian cells in vitro and in vivo. Latex was investigated for its capability of inducing gene mutations and chromosome aberrations in V79 cells in the absence and presence of S9-mix. Concentrations up to 800 micrograms/ml neither induced gene mutations at the HPRT locus nor chromosome aberrations. Latex had no effect on the frequencies of chromosome aberrations in the bone marrow of male and female rats at a dose of 1000 mg/kg. The results indicate that latex of E. milii is not mutagenic in mammalian cells in vitro and in vivo and its use as a molluscicide does not pose a mutagenic hazard for humans.
Assuntos
Látex/toxicidade , Plantas/química , Schistosoma/efeitos dos fármacos , Animais , Biotransformação , Células Cultivadas , Aberrações Cromossômicas , Cricetinae , Cricetulus , Feminino , Hipoxantina Fosforribosiltransferase/genética , Látex/farmacocinética , Masculino , Testes de Mutagenicidade , Ratos , Ratos WistarRESUMO
beta-Myrcene (MYR, 7-methyl-3-methylene-1,6 octadiene) is a peripheral analgesic substance and one of the major constituents of lemongrass oil (Cymbopogon citratus, Stapf), a plant widely used in Brazilian folk medicine. In the present study the genotoxicity of MYR was evaluated in vivo using the rat bone marrow cytogenetic assay. Male and female Wistar rats weighing 250 g (223 to 286 g) and 178 g (168 to 186 g), respectively, were used. Two or four rats of either sex were treated orally with MYR (0.1, 0.5 and 1.0 g/kg po), corn oil (negative control) and cyclophosphamide 30 mg/kg ip (positive control). Animals were sacrificed and bone marrow cells were harvested 24 and 48 h after MYR administration. The mitotic index and the frequency of chromosome aberrations were evaluated. Fifty metaphase cells were examined per animal. A dose related increase in mitotic index was observed 24-h after MYR administration. No evidence of MYR-induced clastogenicity was observed under the experimental conditions of this in vivo assay. The present results and previous negative findings of in vitro mutagenicity tests strongly indicate that MYR is not a genotoxic substance.
Assuntos
Aberrações Cromossômicas , Monoterpenos , Terpenos/toxicidade , Monoterpenos Acíclicos , Animais , Medula Óssea/efeitos dos fármacos , Óleo de Milho/farmacologia , Ciclofosfamida/farmacologia , Feminino , Masculino , Medicina Tradicional , Índice Mitótico , Mutagênese/efeitos dos fármacos , Testes de Mutagenicidade , Óleos Voláteis/toxicidade , Ratos , Ratos Wistar , Fatores de TempoRESUMO
beta-Myrcene (MYR, 7-methyl-3-methylene-1,6 octadiene) is a peripheral analgesic substance and one of the major constituents of lemongrass oil (Cymbopogon citratus, Stapf), a plant widely used in Brazilian folk medicine. In the present study the genotoxicity of MYR was evaluated in vivo using the rat bone marrow cytogenetic assay. Male and female Wistar rats weighing 250 g (223 to 286 g) and 178 g (168 to 186 g), respectively, were used. Two or four rats of either sex were treated orally with MYR (0.1, 0.5 and 1.0 g/kg po), corn oil (negative control) and cyclophosphamide 30 mg/kg ip (positive control). Animals were sacrificed and bone marrow cells were harvested 24 and 48 h after MYR administration. The mitotic index and the frequency of chromosome aberrations were evaluated. Fifty metaphase cells were examined per animal. A dose related increase in mitotic index was observed 24-h after MYR administration. No evidence of MYR-induced clastogenicity was observed under the experimental conditions of this in vivo assay. The present results and previous negative findings of in vitro mutagenicity tests strongly indicate that MYR is not a genotoxic substance