Enhanced response of radioresistant carcinoma cell line to heterogeneous dose distribution of grid; the role of high-dose bystander effect.

Autor: Pakniyat F; Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran, Iran., Nedaie HA; Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran, Iran.; Radiation Oncology Research Center, Cancer institute, Tehran University of Medical Sciences, Tehran, Iran., Mozdarani H; Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran., Mahmoudzadeh A; Department of Bioscience and Biotechnology, Malek-Ashtar University of Technology, Tehran, Iran., Salimi M; Department of Medical genetics, Medical Biotechnology Institute, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran., Griffin RJ; Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Gholami S; Radiation Oncology Research Center, Cancer institute, Tehran University of Medical Sciences, Tehran, Iran.
Jazyk: angličtina
Zdroj: International journal of radiation biology [Int J Radiat Biol] 2020 Dec; Vol. 96 (12), pp. 1585-1596. Date of Electronic Publication: 2020 Nov 12.
DOI: 10.1080/09553002.2020.1834163
Abstrakt: Purpose: The classical dogma that restricted the radiation effect to the directly irradiated cells has been challenged by the bystander effect. This off-target phenomenon which was manifested in adjacent cells via signaling of fully exposed cells might be involved in high-dose Grid therapy as well. Here, an in-vitro study was performed to examine the possible extent of carcinoma cells response to the inhomogeneous dose distribution of Grid irradiation in the context of the bystander effect.
Materials and Methods: Bystander effect was investigated in human carcinoma cell lines of HeLa and HN5 adjacent to those received high-dose Grid irradiation using 'medium transfer' and 'cell-to-cell contact' strategies. Based on the Grid peak-to-valley dose profile, medium transfer was exerted from 10 Gy uniformly exposed donors to 1.5 Gy uniformly irradiated recipients. Cell-contact bystander was evaluated after nonuniform dose distribution of 10 Gy Grid irradiation using cloning cylinders. GammaH2AX foci, micronucleus and clonogenic assays besides gene expression analysis were performed.
Results: Various parameters (ɑ/β, D37, D50) extracted from survival curve which fitted to the Linear Quadratic model, verified more radioresistance of HN5. Survival fraction at 2 Gy (SF2) indicated as 0.42 ± 0.06 in HeLa and 0.5 ± 0.03 in HN5. The level of survival decrease, DNA damages and micronucleus of cells located in the Grid shielded areas (1.5 Gy cell-to-cell contact bystander cells) were significantly more than the values obtained from cells which were irradiated by merely uniform dose of 1.5 Gy. The gH2AX foci and micronuclei frequencies were enhanced in cell-contact bystander approximately more than 1.8 times. Relative expression of DNA damage repair pathway genes ( Xrcc6 and H2afx ) in bystander cells increased significantly. The most cell survival reduction (11.6 times) was revealed in the Grid bystander cells of radioresistant cell line (HN5). No statistically significant difference between 10 Gy uniform beam and Grid non-uniform beam was observed.
Conclusions: Various endpoints confirmed an augmented response of cells in the valley dose region of the Grid block significantly (compared with the cells irradiated by identical dose of uniform beam), suggesting the role of high-dose bystander effect which was more pronounced in resistant carcinoma cell lines. These findings could provide a partial explanation for the Grid beneficial response seen in a number of pre-clinical and clinical studies.
Databáze: MEDLINE
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