RESUMO
The differentiation status of fibroblasts can be characterized by their ability to induce Ah-receptor-dependent genes. The ability to induce Ah-receptor-dependent genes encoding cytochrome P450 isoforms, Ah-receptor repressor, and NADPH-quinine oxidoreductase were studied in the transformed cell clone K8 obtained from immortalized embryonic rat fibroblasts by treatment with benzo(a)pyrene and in the parental clone F27. Treatment with benz(a)anthracene did not induce the genes in the transformed clone K8 on passages 4-14, but the induction was recorded in the transformed clone beginning from the 16th passage and later, whereas in F27 cells the induction was observed throughout the experiment. Induction levels of mRNA of the induction-regulating genes encoding the Ah-receptor and Ah receptor nuclear translocator were similar in F27 cells and in the transformed cell clone K8 in both early and late passages. Electrophoretic mobility shift assay showed that in clone K8 transmission of the induction signal was disturbed in the early passages before interaction of the activated Ah-receptor with the recognizing region of DNA. Possible mechanisms responsible for the absence of induction in the early passages in the transformed cells are discussed.
Assuntos
Técnicas de Cultura de Células , Diferenciação Celular , Fibroblastos/citologia , Regulação da Expressão Gênica , Receptores de Hidrocarboneto Arílico/metabolismo , Animais , Linhagem Celular Transformada , Células Cultivadas , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Embrião de Mamíferos , Fibroblastos/metabolismo , Oxirredutases/genética , Oxirredutases/metabolismo , Ratos , Ratos Endogâmicos F344 , Receptores de Hidrocarboneto Arílico/genéticaAssuntos
Antineoplásicos/farmacologia , Catalase/metabolismo , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Glutationa/metabolismo , Superóxido Dismutase/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa S-Transferase pi , Glutationa Transferase/metabolismo , Humanos , Isoenzimas/metabolismo , Células K562 , Leucemia Eritroblástica Aguda , OxirreduçãoRESUMO
The relationship between expression of genes encoding key antioxidant enzymes, heme oxygenase-1, Bcl-2, and Bcl-xl and change in production of reactive oxygen species (ROS) resulting from development of resistance of cancer cells K562, MCF-7, and SKOV-3 to the prooxidant chemotherapeutic agent doxorubicin (DOX) has been studied. Significant increase in mRNA level and activity of Mn-superoxide dismutase (Mn-SOD), catalase, and selenium-dependent glutathione peroxidase-1 (GPx-1) and reduced ROS level was found in resistant K562/DOX and SKVLB cells. In contrast, no change in ROS level was observed in MCF-7/DOX cells in parallel with decrease in Mn-SOD and catalase mRNAs and corresponding activities concurrently with high increase in GPx-1 mRNA and activity. As a result of the development of resistance, a similarity was found between the change in ROS level and the change in ho-1 and bcl-2 gene expression, whereas elevation of bcl-xl gene expression was observed in all three types of resistant cells. Particular features of development of adaptive antioxidant response as well as redox-dependent change in bcl-2 gene expression under formation of DOX resistance of cancer cells of different genesis are discussed.
Assuntos
Antioxidantes/análise , Doxorrubicina/farmacologia , Heme Oxigenase-1/genética , Neoplasias/enzimologia , Neoplasias/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Espécies Reativas de Oxigênio/análise , Proteína bcl-X/genética , Catalase/análise , Catalase/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glutationa Peroxidase/análise , Glutationa Peroxidase/genética , Heme Oxigenase-1/metabolismo , Humanos , Células K562 , Neoplasias/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/análise , Superóxido Dismutase/análise , Superóxido Dismutase/genética , Proteína bcl-X/metabolismoRESUMO
The article presents the data obtained by the authors in studies of virus-viral co-cancerogenesis, the interaction between some non-oncogenic viruses and well-known oncogenic viruses, the results of co-cancerogenic effect Marek's disease herpesvirus with the avian leukemia virus and the possibility of phenotype mixing between oncornaviruses belonging to different species in nature.