Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Am J Pathol ; 169(4): 1328-42, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17003489

RESUMO

Oxidative stress is a persistent threat to the genome and is associated with major causes of human mortality, including cancer, atherosclerosis, and aging. Here we established a method to generate libraries of genomic DNA fragments containing oxidatively modified bases by using specific monoclonal antibodies to immunoprecipitate enzyme-digested genome DNA. We applied this technique to two different base modifications, 8-hydroxyguanine and 1,N6-propanoadenine (acrotein-Ade), in a ferric nitrilotriacetate-induced murine renal carcinogenesis model. Renal cortical genomic DNA derived from 10- to 12-week-old male C57BL/6 mice, of untreated control or 6 hours after intraperitoneal injection of 3 mg iron/kg ferric nitrilotriacetate, was enzyme digested, immunoprecipitated, cloned, and mapped to each chromosome. The results revealed that distribution of the two modified bases was not random but differed in terms of chromosomes, gene size, and expression, which could be partially explained by chromosomal territory. In the wild-type mice, low GC content areas were more likely to harbor the two modified bases. Knockout of OGG1, a repair enzyme for genomic 8-hydroxyguanine, increased the amounts of acrolein-Ade as determined by quantitative polymerase chain reaction analyses. This versatile technique would introduce a novel research area as a high-throughput screening method for critical genomic loci under oxidative stress.


Assuntos
Adenina/análogos & derivados , Transformação Celular Neoplásica/genética , Mapeamento Cromossômico/métodos , Genes Neoplásicos/genética , Guanina/análogos & derivados , Neoplasias Renais/genética , Estresse Oxidativo , Acroleína/química , Adenina/análise , Adenina/química , Animais , Anticorpos Monoclonais/imunologia , DNA/química , DNA/genética , DNA Glicosilases/genética , Expressão Gênica , Biblioteca Gênica , Genoma/genética , Guanina/análise , Guanina/imunologia , Imunoprecipitação , Rim/química , Masculino , Camundongos , Camundongos Knockout , Oxirredução
2.
Am. j. pathol ; 169(4): 1328-1342, 2006.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP, SESSP-IBACERVO | ID: biblio-1059515

RESUMO

Oxidative stress is a persistent threat to the genome and is associated with major causes of human mortality, including cancer, atherosclerosis, and aging. Here we established a method to generate libraries of genomic DNA fragments containing oxidatively modified bases by using specific monoclonal antibodies to immunoprecipitate enzyme-digested genome DNA. We applied this technique to two different base modifications, 8-hydroxyguanine and 1,N6-propanoadenine (acrotein-Ade), in a ferric nitrilotriacetate-induced murine renal carcinogenesis model. Renal cortical genomic DNA derived from 10- to 12-week-old male C57BL/6 mice, of untreated control or 6 hours after intraperitoneal injection of 3 mg iron/kg ferric nitrilotriacetate, was enzyme digested, immunoprecipitated, cloned, and mapped to each chromosome. The results revealed that distribution of the two modified bases was not random but differed in terms of chromosomes, gene size, and expression, which could be partially explained by chromosomal territory. In the wild-type mice, low GC content areas were more likely to harbor the two modified bases. Knockout of OGG1, a repair enzyme for genomic 8-hydroxyguanine, increased the amounts of acrolein-Ade as determined by quantitative polymerase chain reaction analyses. This versatile technique would introduce a novel research area as a high-throughput screening method for critical genomic loci under oxidative stress.


Assuntos
Masculino , Feminino , Humanos , Animais , DNA , Genética/classificação , Genoma Humano
3.
Oncol Rep ; 12(4): 733-8, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15375492

RESUMO

Carcinogenesis in Thorotrastosis has been assumed due to direct bombardment by alpha-particle with high linear energy transfer during decay of 232Th. To revisit the mechanism of carcinogenesis by Thorotrast (THR), we examined the tissue distribution of THR granules and two-dimensional distribution of radioactivity in the organs of Thorotrastosis patients and studied their spatial relationship to histopathological changes. The high radioactivity in the patients' organ was predominantly derived from decay of Thorium series and showed unique distribution, while the far lower natural radioactivity was mainly from Uranium series decay and fairly evenly distributed. It was found that a large majority of THR granules were phagocytized by macrophages and were embedded in extensive fibrosis. Cancer was rarely in the center of THR deposition but rather at a distance from the deposits. These observations may indicate that the predominant feature of THR deposition is the tissue damage by direct hit of alpha-particles and subsequent fibrosis. The effect of THR resembles action of toxic chemical agents, as several authors have pointed out. We therefore assume that carcinogenesis in Thorotrastosis is a combination of events, such as regeneration of liver tissue after radiation damage, emission of secondary electrons, ionization of the surrounding tissue, and beta- or gamma-ray from daughter nuclei of Thorium (Th). In this context, the role of alpha-particle is important but more intriguing.


Assuntos
Partículas alfa , Fígado/patologia , Fígado/efeitos da radiação , Neoplasias Induzidas por Radiação/etiologia , Dióxido de Tório/farmacocinética , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/etiologia , Carcinoma de Células Escamosas/etiologia , Transformação Celular Neoplásica , Colangiocarcinoma/etiologia , Feminino , Fibrose/etiologia , Raios gama , Humanos , Neoplasias Hepáticas/etiologia , Masculino , Fagocitose , Tório/análise , Distribuição Tecidual
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...