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  • Title: THE DEPENDENCE OF DOSE-EFFECTS IN HUMAN RADIATION CYTOGENETICS.
    Author: Djomina EA.
    Journal: Probl Radiac Med Radiobiol; 2019 Dec; 24():235-249. PubMed ID: 31841470.
    Abstract:
    OBJECTIVE: To study the frequency and spectrum of chromosome aberrations in human peripheral blood lymphocytes depending on the radiation dose, the stage of the mitotic cycle and the periods of fixation of the cell culture. MATERIALS AND METHODS: The test system of blood lymphocytes of donors, the metaphase analysis of chromosome aberrations (a uniform staining of the drugs). The gamma-irradiation was performed on the device with the source 60Co at the dose rate of 0.5 Gy/min, the dose range was 0.25-4.0 Gy. The lymphocyte culture was irradiated after 0, 24, 40 and 48 hours from the beginning of the incubation, which corresponds to G0-, G1-, S-, G2-stages of the mitot- ic cycle. The cells were fixed after 52 hours and 62 hours from the beginning of the incubation. RESULTS: The author's experimental data on the regularities of chromosome aberrations formation during irradiation at the different periods of the mitotic cycle of human lymphocyte culture are presented. The character of the dose dependences of structural damages of chromosomes during the mitotic cycle with an application of the linear, lin- ear-square and parabolic models is analyzed. The greatest yield of exchange-type aberrations is registered at the irradiation in G0- and G1-stages of the mitotic cycle, which submits to the linear-square dependence on an irradia- tion dose. When irradiating cells in the S- and G2-stages, the main contribution to the spectrum of radiation-induced chromosome aberrations is made by deletions, the level of which increases linearly with the dose. This is evidenced by the negative values of the quadratic term in the regression equations for these stages. The analysis of the curves using the parabolic model Y = k · Dn has shown that, at the irradiation of lymphocytes in G0- and G1-stages, the dose dependences approach the quadratic ones, which confirms the reasonableness of the interpretation of the obtained cytogenetic data from the point of view of the «classical» theory of the radiation-induced chromosome aberrations formation. However, the model of the spline regression is more accurate at the approximation of the dependences of the cytogenetic effects in the region of low doses of irradiation. CONCLUSIONS: The results obtained by the irradiation of human lymphocyte culture at different stages of the mitot- ic cycle indicate that the same radiation dose induces different qualitative and quantitative cytogenetic effects depending on the physiological state of the cell at the time of irradiation. The combination of such factors as a radi- ation dose rate, a mitotic cycle stage, the post-irradiation conditions, and an individual radiosensitivity are reflect- ed in quantitative and qualitative variations of the cellular radiosensitivity. Meta: vyvchyty chastotu i spektr aberatsiy̆ khromosom v limfotsytakh peryferychnoï krovi liudyny zalezhno vid dozy oprominennia, stadiï mitotychnogo tsyklu i terminiv fiksatsiï kul'tury klityn.Materialy i metody. Test-systema limfotsytiv krovi donoriv, metafaznyy̆ analiz aberatsiy̆ khromosom (rivnomirne farbuvannia preparativ). Gamma-oprominennia vыpykonano na ustanovtsi z dzherelom 60Co za potuzh- nosti dozy 0,5 Gr/khv, diapazon doz skladav 0,25–4,0 Gr. Kul'turu limfotsytiv oprominiuvaly cherez 0, 24, 40 i 48 god vid pochatku inkubatsiï, shcho vidpovidaie G0-, G1-, S-, G2-stadiiam mytotychnogo tsyklu. Fiksatsiiu klityn provodyly cherez 52 god i 62 god vid pochatku inkubatsiï.Rezul'taty. Vykladeno eksperymental'ni dani avtora shchodo zakonomirnostey̆ utvorennia aberatsiy̆ khromosom pry oprominenni v rizni periody mitotychnogo tsyklu kul'tury limfotsytiv liudyny. Proanalizovano kharakter dozovykh zalezhnostey̆ strukturnykh poshkodzhen' khromosom protiagom mitotychnogo tsyklu iz zastosuvanniam liniy̆noï, liniy̆no-kvadratychnoï i parabolichnoï modeley̆. Nay̆bil'shyy̆ vykhid aberatsiy̆ obminnogo typu reiestruiet'sia pry op- rominenni v G0- i G1-stadiï mitotychnogo tsyklu, iakyy̆ pidporiadkovuiet'sia liniy̆no-kvadratychniy̆ zalezhnosti vid do- zy oprominennia. Pry oprominenni klityn v S- i G2-stadiï osnovnyy̆ vnesok u spektr radiatsiy̆no-indukovanykh abe- ratsiy̆ khromosom vnosiat' deletsiï, riven' iakykh zrostaie liniy̆no z dozoiu. Pro tse svidchat' negatyvni znachennia kvad- ratychnogo chlena v regresiy̆nykh rivnianniakh dlia tsykh stadiy̆. Analiz kryvykh z vykorystanniam parabolichnoï modeli Y = k · Dn pokazav, shcho pry oprominenni limfotsytiv v G0- i G1-stadiï dozovi zalezhnosti nablyzhaiut'sia do kvadra- tychnykh, shcho pidtverdzhuie pravomochnist' interpretatsiï otrymanykh tsytogenetychnykh danykh z pozytsiï «klasychnoï» te- oriï utvorennia radiatsiy̆no-indukovanykh aberatsiy̆ khromosom. Odnak tochnisha aproksymatsiia zalezhnostey̆ tsytoge- netychnykh efektiv v oblasti malykh doz oprominennia dosiagaiet'sia z vykorystanniam modeli splay̆novoï regresiï. Vysnovky. Rezul'taty, otrymani pry oprominenni kul'tury limfotsytiv liudyny v rizni stadiï mitotychnogo tsyklu, svidchat' pro te, shcho odna y̆ ta zh doza radiatsiï indukuie riznyy̆ iakisnyy̆ i kil'kisnyy̆ tsytogenetychnyy̆ efekt zalezh- no vid fiziologichnogo stanu klityny v moment oprominennia. Poiednannia takykh faktoriv, iak velychyna dozy radia- tsiï, stadiia mitotychnogo tsyklu, postpromenevi umovy, indyvidual'na radiochutlyvist', vidobrazhaiet'sia na kil'- kisniy̆ i iakisniy̆ variatsiiakh radiochutlyvosti klityn.
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