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  • Title: СHARACTERISTICS 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.
    Author: Golyarnik NA, Ilienko IN, Zvarych LM, Vorobyov MO, Bazyka DA.
    Journal: Probl Radiac Med Radiobiol; 2021 Dec; 26():357-370. PubMed ID: 34965560.
    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 30persons with malignant neoplasms of the oral cavity, oropharynx and laryngopharynx at III, IVА and IVВ stages ofthe disease. The analysis of parameters of cell cycle and proliferative activity of peripheral blood (PB) lymphocyteswas performed using the flow cytometry. The evaluation of distribution of cells by G0/G1, S, G2/M cell cycle phaseswas done in vivo and in in vitro. Proliferative potential was analyzed by level of expression of cytoplasmic protein ofcyclin D1. RESULTS: Proliferative potential of PB lymphocytes of Chornobyl clean"up workers and persons with malignant neo"plasms of the oral cavity, oropharynx and laryngopharynx was assessed. An increase in the level of spontaneousсyclin D1 expression and disturbance of сyclin D1-dependent regulation of cell cycle of PB lymphocytes after mito"gen 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 changesare most pronounced in the subgroup of persons with a radiation dose of D > 500 mSv, and in persons with oncolo"gical pathology. CONCLUSIONS: A positive linear dependence has been established between the radiation dose and the number of cellsin 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. Meta. Doslidyty osoblyvosti proliferatyvnogo potentsialu limfotsytiv peryferychnoï krovi uchasnykivlikvidatsiï naslidkiv avariï na ChAES ta osib, khvorykh na zloiakisni novoutvorennia porozhnyny rota, rotovoï ta gor"tannoï chastyn glotky, za rivnem ekspresiï tsyklinu D1 ta kil'kisnymy pokaznykamy klitynnogo tsyklu.Materialy i metody. Obstezheno 294 cholovikiv u vitsi (58,47 ± 7,32) rokiv, sered nykh: 215 uchasnykiv likvidatsiïnaslidkiv avariï (LNA) na ChAES 1986–1987 rr., dozy zovnishn'ogo oprominennia 10,43–3623,31 mZv; 49 osib kont"rol'noï grupy ta 30 khvorykh na zloiakisni novoutvorennia porozhnyny rota, rotovoï ta gortannoï chastyn glotky III,IVA ta IVV stadiĭ zakhvoriuvannia. Analiz parametriv klitynnogo tsyklu i proliferatyvnoï aktyvnosti limfotsytivperyferychnoï krovi (PK) provodyly metodom protochnoï tsytometriï. Otsiniuvaly rozpodil klityn po G0/G1", S" iG2/M"fazakh klitynnogo tsyklu v umovakh in vivo ta in vitro. Proliferatyvnyĭ potentsial analizuvaly za rivnemekspresiï tsytoplazmatychnogo bilka tsyklinu D1.Rezul'taty. Provedeno otsinku proliferatyvnogo potentsialu limfotsytiv PK uchasnykiv likvidatsiï naslidkivavariï na ChAES ta osib, khvorykh na zloiakisni novoutvorennia porozhnyny rota. V uchasnykiv LNA na ChAES vyznache"no pidvyshchennia rivnia spontannoï ekspresiï tsyklinu D1 ta porushennia tsyklin D1"zalezhnoï reguliatsiï klitynnogotsyklu limfotsytiv PK pislia aktyvatsiï mitogenom. Vyznacheno zbil'shennia pulu klityn u S" ta G2/M"fazakh klityn"nogo tsyklu, shcho kharakteryzuie vysokyĭ proliferatyvnyĭ potentsial limfotsytiv PK. Dani zminy naĭbil'sh vyra"zheni u pidgrupi osib, oprominenykh v dozi D > 500 mZv, ta u patsiientiv z onkologichnoiu patologiieiu. Vysnovky. Vstanovleno pozytyvnu liniĭnu zalezhnist' mizh dozoiu oprominennia ta kil'kistiu klityn S"fazyklitynnogo tsyklu u pidgrupi uchasnykiv LNA na ChAES, oprominenykh u dozakh D > 500 mZv. Vyiavleni zminy tsyklin D1"zalezhnoï reguliatsiï klitynnogo tsyklu ta proliferatyvnogo statusu limfotsytiv zalezhat' vid dozy oprominennia,mozhut' buty proiavom nestabil'nosti genomu i sprychyniaty ryzyky onkogenezu u viddalenomu periodi pislia op"rominennia.
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