Characteristics of Cyclin D1-Mediated Regulation of Cell Cycle of Peripheral Blood Limphocytes of Chornobyl Clean-Up Workers and Persons With Malignant Neoplasms of the Oral Cavity, Oropharynx and Laryngopharynx

Abstract

Objective: to explore proliferative potential of peripheral blood lymphocytes of Chornobyl clean-up workers and persons with malignant neoplasms of the oral cavity, oropharynx and laryngopharynx by level of expression of cyclin D1 and quantitative parameters of cell cycle. Materials and methods. A total of 294 men aged (58.47 ± 7.32) were surveyed, 215 of them were Chornobyl clean-up workers (1986–1987), exposed at the dose range 10.43–3623.31 mSv; 49 persons of the control group and 30 persons with malignant neoplasms of the oral cavity, oropharynx and laryngopharynx at III, IVА and IVВ stages of the disease. The analysis of parameters of cell cycle and proliferative activity of peripheral blood (PB) lymphocytes was performed using the flow cytometry. The evaluation of distribution of cells by G0/G1, S, G2/M cell cycle phases was done in vivo and in in vitro. Proliferative potential was analyzed by level of expression of cytoplasmic protein of cyclin D1. Results. Proliferative potential of PB lymphocytes of Chornobyl clean-up workers and persons with malignant neoplasms of the oral cavity, oropharynx and laryngopharynx was assessed. An increase in the level of spontaneous сyclin D1 expression and disturbance of сyclin D1-dependent regulation of cell cycle of PB lymphocytes after mitogen activation were determined in the Chornobyl clean-up workers. An increase in pool of cells in the S- and G2/M-phases of cell cycle was detected, which characterizes high proliferative potential of PB lymphocytes. These changes are most pronounced in the subgroup of persons with a radiation dose of D < 500 mSv, and in persons with oncological pathology. Conclusions. A positive linear dependence has been established between the radiation dose and the number of cells in the S-phase of cell cycle in the subgroup of Chornobyl clean-up workers with a radiation dose of D < 500 mSv. The detected changes of cyclin D1-dependent regulation of cell cycle and proliferative status of lymphocytes depend on the radiation dose, can be a manifestation of genome instability and be a cause for risks of oncogenesis, in a remote period after radiation exposure. Key words: cell cycle, cyclin D1, oncological pathology, radiation, Chornobyl.