RESUMO
Aberrant methylation of regulation regions of tumorsuppressor genes is showed for many cancer diseases. In course of this modification an enzyme DNMT3 methylates RCGY sites in CpG-islands of regulation regions producing R(5mC)GY sites. Earlier we developed GLAD-PCR assay to determine R(5mC)GY site in a definite position of human genome. In this work we have applied GLAD-PCR assay to determine R(5mC)GY sites in regulation regions of ESR1 and ELMO1 tumor-suppressor genes. We have studied a fragment of first exon of ELMO1 gene and a part of ESR1 promoter region in DNA preparations from malignant cell line SW837 and colorectal tumor samples. We have checked four sites in each region and found two highly methylated sites: GCGC in first exon of ELMO1 gene and GCGT in promoter region of ESR1 gene. Site GCGT is weakly methylated in healthy tissues and more methylated in the most of colorectal samples. Site GCGC is not methylated in healthy tissues and significantly methylated in 60% of colorectal samples. A possibility to use GLAD-PCR assay for cancer diagnostics is discussed.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Colorretais/genética , Metilação de DNA , DNA de Neoplasias/genética , Receptor alfa de Estrogênio/genética , Reação em Cadeia da Polimerase/métodos , Sequências Reguladoras de Ácido Nucleico , Proteínas Supressoras de Tumor/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , DNA de Neoplasias/metabolismo , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Masculino , Proteínas Supressoras de Tumor/metabolismoRESUMO
The characteristic of medical and dosimetric register database of Siberian Group of Chemical Enterprises personnel is represented. This characteristic includes the description of the database structure, main sources of information, quantitative composition of the cohort under study, methods of evaluation of the external and internal irradiation doses, modern data on cancer incidence and reasons of death. The database is the basis for estimating the risk of the cancer and non-cancer effects after a long-term radiation exposure and dependence of "dose-response" at different levels: from population and group to cell and molecular. Now the database of register contains the information about more than 66,500 employees at the Siberian Group of Chemical Enterprises, about 22,000 of whom were exposed to external irradiation and more than 7500 employees--to internal irradiation. The register is the information resource of a large biological material bank. Using this bank, the research of chronic radiation exposure genetic effects and markers of individual radio sensitivity is performed.
