Cell cycle perturbations and genotoxic effects in human primary fibroblasts induced by low-energy protons and X/gamma-rays.
Cell cycle perturbations and genotoxic effects in human primary fibroblasts induced by low-energy protons and X/gamma-rays.
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低能质子和 X/γ 射线诱导的人原代成纤维细胞的细胞周期扰动和基因毒性效应。
DOI：
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发表时间：
2009
影响因子：
2
通讯作者：
C. Tanzarella
中科院分区：
文献类型：
--
作者：
A. Antoccia;A. Sgura;F. Berardinelli;M. Cavinato;R. Cherubini;S. Gerardi;C. Tanzarella
在正常人成纤维细胞中研究了梯度剂量的高线性能量转移（LET）低能质子诱导周期扰动和遗传毒性损伤的作用。此外，这种影响进行了比较，由低LET辐射所产生的。HFFF 2，人原代成纤维细胞暴露于质子（LET = 28.5 keV/microm）或X/γ射线，并分析与细胞周期动力学和DNA损伤相关的终点。在两种类型的照射后，非同步化的细胞在1-4戈伊的剂量下受到进入S期的抑制，并在G（1）期停留数天。TP 53和CDKN 1A等调节蛋白的诱导水平表现出明显的LET依赖性。通过对γ-H2 AX病灶评分测量的DSB诱导和修复表明，相对于X射线，质子产生的DSB数量较少/戈伊，这显示出消失的动力学较慢。这一结果与X射线照射后双核细胞MN的诱导程度一致。克隆形成试验表明，两种辐射无显著差异，但γ射线曲线的斜率比质子曲线的斜率大。总之，在正常人原代成纤维细胞中，细胞周期停滞在G（1）/S转换可以在照射后不久触发，并在质子和X射线照射后维持数小时。由质子产生的DNA损伤似乎不太容易修复，并且可以以MN的形式转化为细胞遗传学损伤。
The effect of graded doses of high-linear energy transfer (LET) low-energy protons to induce cycle perturbations and genotoxic damage was investigated in normal human fibroblasts. Furthermore, such effects were compared with those produced by low-LET radiations. HFFF2, human primary fibroblasts were exposed to either protons (LET = 28.5 keV/microm) or X/gamma-rays, and endpoints related to cell cycle kinetics and DNA damage analysed. Following both type of irradiations, unsynchronized cells suffered an inhibition to entry into S-phase for doses of 1-4 Gy and remained arrested in the G(1)-phase for several days. The levels of induction of regulator proteins, such as TP53 and CDKN1A showed a clear LET-dependence. DSB induction and repair as measured by scoring for gamma-H2AX foci indicated that protons, with respect to X-rays, yielded a lower number of DSBs per Gy, which showed a slower kinetics of disappearance. Such result was in agreement with the extent of MN induction in binucleated cells after X-irradiation. No significant differences between the two types of radiations were observed with the clonogenic assay, resulting anyway the slope of gamma-ray curve higher than that the proton one. In conclusion, in normal human primary fibroblasts cell cycle arrest at the G(1)/S transition can be triggered shortly after irradiation and maintained for several hours post-irradiation of both protons and X-rays. DNA damage produced by protons appears less amenable to be repaired and could be transformed in cytogenetic damage in the form of MN.
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影响因子：
3.7
作者：
NODA, A;NING, Y;SMITH, JR
通讯作者：
SMITH, JR
影响因子：
3.8
作者：
Mukherjee, Bipasha;Camacho, Cristel Vanessa;Burma, Sandeep
通讯作者：
Burma, Sandeep
影响因子：
2.6
作者：
WARD, JF
通讯作者：
WARD, JF
影响因子：
2.6
作者：
Ianzini, F;Mackey, MA
通讯作者：
Mackey, MA