SELECTION AND TESTING OF EXPERIMENTAL MODELS OF NORMAL AND MALIGNANT HUMAN CELLS IN VITRO AND EVALUATION OF THEIR SENSITIVITY RANGE TO THE NEUTRON/CAPTURE AND PHOTON/CAPTURE AGENTS AND PHOTOSENSITIZERS.

O D Pochapinskyi, G Yo Lavrenchuk, N P Atamaniuk, A V Chernyshov
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Abstract

Objective: to investigate the structural and morpho-functional changes in test systems of malignant (A-549 cellline) and normal (fibroblasts of the 6th passage) human cells during incubation with gadolinium-containing pho-ton-capture agent «Dotavist» and photosensitizer «Fotolon».

Methods: The passaged (continuously interweaved) cell culture technique on normal human fibroblasts and malig-nant human cells; cytological, biophysical, statistical methods.

Results: The cytotoxic properties of «Dotavist» gadolinium-containing photon-capturing agent and «Photolon»photosensitizer in a wide range of concentrations (5, 10, 25, 50, 100 and 200 μl/ml) were studied by the morpho-functional characteristics (growth kinetics, proliferative and mitotic activity, presence of atypical cells) in the invitro test systems of malignant (non-small cell lung cancer cell line A-549) and normal (6th passage fibroblasts)human cells. It was found that the cytotoxic properties of «Dotavist» in test systems of malignant and normal cellsare expressed under its administration in high concentrations (100 and 200 μl/ml). During incubation with«Photolon» photosensitizer the cytotoxic effect on malignant cells was determined at the lowest concentrations (5and 10 μl/ml). Photosensitizer administration in the increasing concentrations has lead to genotoxic effects.Cytotoxic effect of photosensitizer on the normal human fibroblasts was evident in the 5-200 μl/ml concentrationrange. There was a moderate decrease in mitotic activity along with increasing concentration. Genotoxic propertiesof photosensitizer were evident at 25 μl/ml concentration and above.

Conclusion: Study results of the effectiveness of neutron-capture and photon-capture technologies by the sensi-tivity assay in the in vitro test systems of human malignant cells (non-small cell lung cancer cell line A-549) andnormal cells (transplantable human fibroblast culture, the 6th passage) to the gadolinium-containing photon-cap-ture «Dotavist» agent and «Photolon» photosensitizer in different concentrations provide the basis for pre-clinicalstage of evaluating the effectiveness of medications used in binary technologies.

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正常和恶性人体细胞体外实验模型的选择和测试及其对中子/捕获剂和光子/捕获剂及光敏剂的敏感性范围的评价。
目的:探讨含钆光捕获剂Dotavist和光敏剂Fotolon对人恶性细胞(A-549细胞系)和正常细胞(第6代成纤维细胞)的结构和形态功能的影响。方法:对正常人成纤维细胞和恶性人细胞进行传代(连续交织)培养;细胞学、生物物理学、统计学方法。结果:在恶性(非小细胞肺癌细胞系a -549)和正常(第6代成纤维细胞)人细胞的体外实验系统中,通过形态功能特征(生长动力学、增殖和有丝分裂活性、非典型细胞的存在)研究了不同浓度(5、10、25、50、100和200 μl/ml)的“Dotavist”含钆光子捕获剂和“Photolon”光敏剂的细胞毒性。结果表明,在高浓度(100 μl/ml和200 μl/ml)作用下,“dodoavist”在恶性细胞和正常细胞的实验系统中均表现出细胞毒性。在与«Photolon»光敏剂孵育期间,在最低浓度(5和10 μl/ml)下测定了对恶性细胞的细胞毒作用。增加光敏剂浓度会导致遗传毒性作用。光敏剂在5 ~ 200 μl/ml浓度范围内对正常人成纤维细胞有明显的细胞毒作用。随着浓度的增加,有丝分裂活性有中度下降。光敏剂在25 μl/ml及以上浓度时具有明显的遗传毒性。结论:通过对人恶性细胞(非小细胞肺癌细胞系A-549)和正常细胞(可移植人成纤维细胞培养)体外试验系统中中子捕获和光子捕获技术有效性的敏感性试验研究结果不同浓度的含钆光子捕获剂“Dotavist”和“Photolon”光敏剂为评估二元技术中使用的药物有效性的临床前阶段提供了基础。
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Problemy radiatsiinoi medytsyny ta radiobiolohii
Problemy radiatsiinoi medytsyny ta radiobiolohii Medicine-Radiology, Nuclear Medicine and Imaging
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