Genetic instability profile in individuals exposed to low doses of ionizing radiation: A pilot study

Introduction. Ionizing radiation is a mutagen that exerts a significant impact on the hematopoietic system. It is hypothesized that the initiating link in radiation-induced pathological processes, including the development of clonal hematopoiesis and subsequent malignant transformation, is genetic instability in hematopoietic stem cells. However, the effects of low radiation doses on the hematopoietic system remain insufficiently studied, which complicates the assessment of long-term risks for occupational groups (medical personnel, nuclear power plant workers) and the population exposed to chronic low-dose irradiation.

Objective. To assess genetic instability in nuclear industry workers with prolonged exposure to low-dose ionizing radiation.

Materials and methods. A prospective single-center study included 35 nuclear power plant workers (80% male, mean age 53 years) with documented occupational exposure to low doses (mean annual effective dose 1.34 mSv). In 15 participants, cytogenetic analysis (assessment of spontaneous chromosomal aberrations) and targeted high-throughput sequencing of a panel of 118 genes associated with clonal hematopoiesis were performed.

Results. An extremely high level of genetic risk (> 10 cytogenetic aberrations) was identified in 53% of the examined individuals (median 68, range: 14–257). By next-generation sequencing, 82 mutations were detected in 45 driver genes of clonal hematopoiesis (median 8 mutations per person), of which 7% (n = 6) were classified as pathogenic or likely pathogenic for hematological diseases. The most frequently mutated genes were RYR1 (10%), ARID1A, KMT2C, and KMT2D (5% each). G > A and C > T substitutions predominated. In one patient with high genetic risk (40 years of service, VAF 52.6% in the TET2 gene), leukopenia of undetermined significance was diagnosed during a 24-month follow-up period.

Conclusions. Prolonged occupational exposure to low doses of ionizing radiation induces a clastogenic effect and necessitates monitoring of genetic instability in exposed personnel. Further research should be focused on the mechanisms of action of low-dose ionizing radiation, identification of biomarkers of individual radiosensitivity, and development of cohort-oriented programs for the prevention of radiation-induced hematological neoplasms.

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