ABSTRACT
We studied the effect of technogenic radiation on the degree of promoter methylation in genes involved in apoptosis in blood lymphocytes of workers exposed to long-term γ-radiation during their professional activities. Blood samples for the analysis were obtained from 11 conventionally healthy men aged from 54 to 71 years (mean 66 years), workers of the Siberian Group of Chemical Enterprises working experience from 27 to 40 years (mean 30 years); the external exposure dose was 175.88 mSv (158.20-207.81 mSv). In all examined subjects, the degree of methylation of the promoters of apoptosis-related genes ranged from 0.22 to 50.00%. A correlation was found between the degree of methylation of BCLAF1 promoters (p=0.035) with the age of workers, BAX promoters (p=0.0289) with high content of aberrant cells, and APAF1 promoters (p=0.0152) with increased number of dicentric chromosomes. A relationship was found between the dose of external irradiation and the degree of methylation of gene promoters of BAD (p=0.0388), BID (Ñ=0.0426), and HRK (Ñ=0.0101) genes.
Subject(s)
Chromosome Aberrations/radiation effects , DNA Methylation , Epigenesis, Genetic , Lymphocytes/radiation effects , Occupational Exposure/adverse effects , Promoter Regions, Genetic , Radiation Exposure/adverse effects , Aged , Apoptosis/genetics , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Apoptotic Protease-Activating Factor 1/genetics , Apoptotic Protease-Activating Factor 1/metabolism , BH3 Interacting Domain Death Agonist Protein/genetics , BH3 Interacting Domain Death Agonist Protein/metabolism , Chromosome Aberrations/classification , Gamma Rays/adverse effects , Humans , Lymphocytes/metabolism , Lymphocytes/pathology , Male , Middle Aged , Radiometry , Repressor Proteins/genetics , Repressor Proteins/metabolism , Siberia , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolism , bcl-Associated Death Protein/genetics , bcl-Associated Death Protein/metabolismABSTRACT
The results of the study of frequency and spectrum of cytogenetic anomalies in 657 healthy employees of the main facilities of the Siberian Group of Chemical Enterprises exposed to external, internal and combined irradiation are presented. No dependence between age and chromosome aberrations frequency was revealed. Chronic external exposure appeared to be the main factor of induction of chromosome aberrations. The frequency of aberrant cells, chromosome type aberrations, paired fragments and rings was statistically significantly higher in employees exposed to external irradiation as compared to persons exposed to combined irradiation. A nonlinear dependence the dose of irradiation and frequency of chromosome aberrations was revealed. A statistically significant decrease of prevalence of aberrant cells, aberration of chromatid and chromosome type was established in employees exposed to irradiation at a dose range of > 0-10 mSv compared to the control group. This agrees with the phenomenon of radiation hormesis. A significant increase of the frequency of chromosome aberrations was not observed at doses below > 40 mSv. In employees exposed to irradiation at a dose range > 40-100 mSv, a statistically significant increase of frequencies of aberrant metaphases, aberrations of chromatid and chromosome types was established. Same was found for dicentrics at dose range of >100-200 mSv. This supports a well known linear threshold model. Dose-effect curve has a plateau at doses ranged from 100 to 500 mSv.
