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Spectrum of TP53 Sequence Variants on Chronically Exposed Humans

  • V. S. Nikiforov,
  • A. V. Korechenkova,
  • A. V. Akleyev

摘要

It is known that ionizing radiation can damage the genetic apparatus of a cell not only through direct exposure, but also through the induction of oxidative stress. Thus, oxidation of guanine (G) nitrogenous base by oxidative stress products can result in G:C>T:A and G:C>C:G type transversions in the tumor growth suppressor gene TP53. Somatic and inherited variants of the TP53 gene, in turn, are of great importance in the development of malignant neoplasms. Therefore, the aim of the study was to analyze the G:C>T:A and G:C>C:G transversions of the TP53 gene in peripheral blood cells of individuals affected by chronic low-dose rate exposure. The paper presents the results of the analysis of the spectrum of TP53 gene sequence variants based on G:C>T:A and G:C>C:G transversions in peripheral blood cells of the Techa Riverside residents of the Chelyabinsk and Kurgan regions affected by chronic low-dose exposure in the 1950s. The range of individual values of the accumulated absorbed dose to red bone marrow due to external gamma radiation and 90Sr ranged from 2.1 to 2742.0 mGy (mean value being 605.4 ± 191.9 mGy (M ± SE)). As a result of the study, 7 different variants of the TP53 gene based on the G:C>T:A and G:C>C:G transversions, which are single-nucleotide substitutions, were identified in the examined individuals. All detected variants were present in the IARC TP53 Database and had no clinical significance as “pathogenic” or “probably pathogenic.” The differences in the frequencies of carriers of detected TP53 gene variants between the comparison group and the main group did not reach a statistically significant level.