Effect of an ATM Kinase Inhibitor on Thermo-and / or Radio-sensitization in Non-proliferating Normal Human Fibroblasts and Osteosarcoma Cells
Effect of an ATM Kinase Inhibitor on Thermo-and / or Radio-sensitization in Non-proliferating Normal Human Fibroblasts and Osteosarcoma Cells
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ATM 激酶抑制剂对非增殖正常人成纤维细胞和骨肉瘤细胞热敏化和/或放射敏化的影响
DOI：
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Hisao Ito
中科院分区：
文献类型：
--
作者：
Kohei Inoue;T. Kawata;M. Saito;Cuihua Liu;T. Uno;K. Isobe;Hisao Ito
本文所述工作的目的是确定共济失调-毛细血管扩张突变蛋白（ATM）激酶抑制剂对正常人成纤维细胞和骨肉瘤细胞在细胞生长的平台期或融合期的热敏感性和/或放射敏感性的影响。在存在或不存在ATM激酶抑制剂的情况下，当细胞暴露于45°C的热休克和/或γ射线时，观察到细胞存活和染色体畸变。用集落形成测定法测量细胞存活。用化学诱导的染色体早熟凝集和荧光原位杂交观察染色体畸变。在45°C下热休克处理增强了两种细胞系的细胞放射敏感性。加入ATM激酶抑制剂放大了这种效应。此外，通过用ATM激酶抑制剂处理，两种细胞系在45°C下的热敏性增强。在45°C下的热休克处理增强了两种细胞系中由γ辐射诱导的染色体畸变的频率;在ATM激酶抑制剂存在下，染色体畸变的频率增强。因此，ATM激酶抑制剂增加了热诱导畸变的数量。在正常人成纤维细胞和骨肉瘤细胞中均观察到这些结果。ATM激酶抑制剂可在细胞生长的平台期或汇合期促进热诱导的细胞杀伤和热诱导的细胞染色体畸变频率。
This aim of the work described here was to determine the effect of an ataxia-telangiectasia mutated protein (ATM) kinase inhibitor on thermo-and/or radio-sensitivity in normal human fibroblasts cells and in osteosarcoma cells in the plateau or confluent phase of cell growth. Cell survival and chromosome aberrations were observed when cells were exposed to a heat shock at 45°C and/or γ-rays in the presence or absence of an ATM kinase inhibitor. Cell survival was measured with colony formation assays. Chromosome aberrations were observed using chemically induced premature chromosome condensation and fluorescence in situ hybridization. Cellular radiosensitivity was enhanced in both cell lines by a heat shock treatment at 45°C. Adding an ATM kinase inhibitor amplified this effect. Furthermore, thermosensitivity in both cell lines at 45°C was enhanced by treatment with an ATM kinase inhibitor. Heat shock treatments at 45°C enhanced the frequency of chromosome aberrations induced byγ-irradiation in both cell lines;in the presence of an ATM kinase inhibitor, the frequency of chromosome aberrations was enhanced. Thus, ATM kinase inhibitors increased the number of heat-induced aberrations. These results were observed in both,normal human fibroblasts cells and osteosarcoma cells. ATM kinase inhibitors can contribute to heat-induced cell killing and to heat-induced cellular chromosome aberration frequencies in the plateau or confluent phase of cell growth.
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影响因子：
2.6
作者：
Wong,RS;Dynlacht,JR;Cedervall,B;Dewey,WC
通讯作者：
Dewey,WC
DOI：
--
发表时间：
--
期刊：
Environmental Science and Pollution Research International
影响因子：
--
作者：
P. Wust;B. Hildebrandt;G. Sreenivasa;B. Rau;J. Gellermann;H. Riess;R. Felix;P. Schlag
通讯作者：
P. Wust;B. Hildebrandt;G. Sreenivasa;B. Rau;J. Gellermann;H. Riess;R. Felix;P. Schlag
影响因子：
11.2
作者：
Hunt, Clayton R.;Pandita, Raj K.;Pandita, Tej K.
通讯作者：
Pandita, Tej K.
影响因子：
4.2
作者：
T. Pandita;J. R. Roti Roti-J.-R.-Roti-Roti-7707447
通讯作者：
T. Pandita;J. R. Roti Roti-J.-R.-Roti-Roti-7707447
影响因子：
56.9
作者：
CORNFORTH, MN;BEDFORD, JS
通讯作者：
BEDFORD, JS