Ilienko I. Gene regulation of apoptosis, proliferation and aging of human immune cells in the early and remote periods after radiation exposure.

In dissertation, a concept is elaborated of the modifying influence of ionizing radiation on gene regulation of immune cells apoptosis, proliferation and aging in a group of Chornobyl cleanup workers exposed to a wide range of doses and personnel exposed to occupational limits. According to the proposed concept development of immune deficiency and increased risk of cell transformation in a remote period after exposure are associated with dose dependent violations of gene regulation of the basic mechanisms of cellular homeostasis. The changes included an incompleteness of apoptosis in doses over 500 mSv with imbalance in the expression of pro- and antiapoptotic genes; cellular aging and TERT-associated risk of immune cells transformation due to TP53-mediated regulation; violations of cyclin-kinase cell cycle regulation, differentiation and signal transduction; preserved radiogenic TCR mutations and genes overexpression in the effector lymphocyte subsets (CD16+CD57+, HLA-DR+). In the early period after exposure in occupational limits of 20 mSv the activation of protective and compensatory processes together with the signs of initiation of the immune cells radiation aging were demonstrated with an increased apoptosis, changes in gene regulation of telomere-telomerase complex and overexpression of antigens associated with antiviral and anti-tumor immune surveillance.