RESUMO
Praziquantel, a drug used for the treatment of neurocysticercosis, was tested for its ability to induce morphological transformation of Syrian hamster embryo fibroblasts. Results indicate that praziquantel transforms these cells without affecting their viability. Further experiments were carried out to investigate its possible mechanism of action in the same cell system. Micronucleus formation was observed in cultures treated with concentrations which induced morphological transformation, about 40% of these micronuclei were positive to a kinetochore antibody. No induction of DNA repair synthesis was observed even at cytotoxic concentrations. These results suggest that praziquantel has an aneugenic effect which could be responsible for its ability to transform morphologically these cells. Risk-benefit analysis should be carried out whenever this drug is utilized.
Assuntos
Carcinógenos/toxicidade , Testes para Micronúcleos , Mutagênicos/toxicidade , Praziquantel/toxicidade , Animais , Linhagem Celular , Linhagem Celular Transformada , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , DNA/biossíntese , DNA/efeitos dos fármacos , Reparo do DNA , Embrião de Mamíferos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Mesocricetus , Timidina/metabolismoRESUMO
In chronic helminthic infections such as cysticercosis, where the parasites live for years, profound modulation of the host immune response has been reported. To evaluate the genotoxicity of a drug used to treat cysticercosis, we observed the occurrence of genetic damage in cultured lymphocytes from cysticercotic swine and patients who had not been exposed to the drug. The human lymphocytes also showed a slower proliferation. These data suggested that the disease itself was promoting genetic damage in host lymphocytes which, in part, could explain the retardation of the lymphocyte proliferation observed in cysticercotic patients. Pigs infected with Taenia solium cysticerci showed an increased lymphocyte proliferation for 6-8 weeks post infection, followed by an impaired proliferation after this period. Significant induction of sister-chromatid exchanges was also observed in lymphocytes from infected pigs after the 6th week post infection. Additionally, it was found that a factor secreted by the cysticerci morphologically transformed primary fibroblasts in culture. The results strongly suggest that the parasite produces genetic instability in the host cells, which could result in immunosuppression and malignant transformation of target cells.
Assuntos
Cisticercose/genética , Cisticercose/imunologia , Ativação Linfocitária , Linfócitos/imunologia , Troca de Cromátide Irmã , Animais , Divisão Celular , Linhagem Celular , Transformação Celular Neoplásica , Células Cultivadas , Cricetinae , Embrião de Mamíferos , Embrião não Mamífero , Humanos , Mesocricetus , Suínos , Taenia/patogenicidade , Fatores de TempoRESUMO
The insecticide buprofezin was examined for its genotoxicity in cultured Syrian hamster embryo cells in order to better understand the mechanisms underlying the genotoxicity of the compound in mammalian cells. Exposure to buprofezin concentrations of 12.5-100 microM did not significantly affect the colony-forming ability of the cells, but did result in increased frequencies of morphologically transformed colonies. Treatment with buprofezin did not cause a detectable induction of DNA repair synthesis, an indicator of DNA damage, but significantly increased the frequency of micronuclei. Immunostaining of the cells with antikinetochore antibody (CREST antibody) showed that essentially all of the buprofezin-induced micronuclei were kinetochore-positive. The results suggest that morphological transformation of Syrian hamster embryo cells by buprofezin results from an interaction of the compound or a metabolite of it with the mitotic apparatus rather than from DNA damage.
Assuntos
Transformação Celular Neoplásica , Dano ao DNA , Inseticidas/toxicidade , Mutagênicos/toxicidade , Tiadiazinas/toxicidade , Animais , Células Cultivadas , Centrômero , Cricetinae , Mesocricetus , Testes para Micronúcleos , Microtúbulos , Estrutura MolecularRESUMO
Generation of triplet ketones, either chemically through thermal decomposition of 3-hydroxymethyl-3,4,4-trimethyl-1,2-dioxetane and 3-[N-(pyridino)carbamoyl]methyl-3,4,4-trimethyl-1,2-dioxetane++ + or enzymatically via the aerobic oxidation of isobutyraldehyde trimethylsilyl enol ether catalyzed by horse-radish peroxidase, triggers the SOS function sfiA in E. coli. Although the observed effects are relatively weak and the triplet ketone scavenger tryptophan was ineffective in this system, our results provide evidence for the involvement of triplet ketones in this type of DNA damage. Possible mechanisms are discussed.