Gene hypermethylation in blood leukocytes in humans long term after radiation exposure – Validation set
| Autor: | Tamara V. Azizova, Nellya Sh. Lapteva, Natalya S. Vyazovskaya, G. G. Rusinova, Nina S. Kuzmina, Rubanovich Av |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine Premature aging Time Factors Adolescent Health Toxicology and Mutagenesis Gene Expression Biology Toxicology Epigenesis Genetic Ionizing radiation Andrology Young Adult 03 medical and health sciences GSTP1 0302 clinical medicine Leukocytes Humans Epigenetics Child Promoter Regions Genetic Gene Cyclin-Dependent Kinase Inhibitor p16 Aged Aged 80 and over Promoter General Medicine DNA Methylation Middle Aged Radiation Exposure Pollution 030104 developmental biology Glutathione S-Transferase pi CpG site Child Preschool 030220 oncology & carcinogenesis DNA methylation CpG Islands Female |
| Zdroj: | Environmental Pollution. 234:935-942 |
| ISSN: | 0269-7491 |
| Popis: | Hypermethylation of СpG islands in the promoter regions of several genes with basic protective function in blood leukocytes of individuals exposed to ionizing radiation long time ago (2–46 years), and differential effects of age and radiation exposure on hypermethylation was reported in our previous work. To validate these results, epigenetic modifications were assessed in an independent series of 49 nuclear industry workers from the “Mayak” facility (67–84 years old at sampling) with documented individual accumulated doses from the prolonged external γ-radiation exposure (95.9–409.5 cGy, end of work with radiation:0.3–39 years ago), and in 50 non-exposed persons matched by age. In addition to the genes analyzed before (RASSF1A, p16/INK4A, p14/ARF, GSTP1), four additional loci were analyzed: TP53, ATM, SOD3, ESR1. The frequency of individuals displaying promoter methylation of at least one of the 8 genes (71.4%) was significantly higher in exposed group as compared to the control group (40%), p = .002, OR = 3.75. A significantly elevated frequency of individuals with hypermethylated СpG islands in GSTP1, TP53, SOD3 promoters was revealed among exposed subjects as compared to the control group (p = .012, OR = 8.41; p = .041, OR = 4.02 and p = .009, OR = 3.42, respectively). A similar trend (p = .12, OR = 3.06) was observed for the p16/INK4A gene. As a whole, p16/INK4A and GSTP1 promoter hypermethylation in irradiated subjects from both previously and currently analyzed groups was pronounced. Thus, the direction of the effects was fully confirmed, suggesting the result reproducibility. No statistically significant correlation between promoter methylation and individual radiation dose was found. Further studies are required to create an array of blood epigenetic markers of radiation exposure associating with premature aging and age-related diseases and to accurately evaluate radiation-added effect across the range of doses. Synthesis The results of studies of epigenetic changes in two independent samples of irradiated subjects indicated the significance of radiation factor in the induction of hypermethylation of CpG islands in gene promoters that is revealed in blood cells years and decades after exposure. |
| Databáze: | OpenAIRE |
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