Assessment of targeted and non-targeted responses in cells deficient in ATM function following exposure to low and high dose X-rays.
Assessment of targeted and non-targeted responses in cells deficient in ATM function following exposure to low and high dose X-rays.
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DOI：
10.1371/journal.pone.0093211
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Lindholm C
中科院分区：
文献类型：
--
作者：
Kiuru A;Kämäräinen M;Heinävaara S;Pylkäs K;Chapman K;Koivistoinen A;Parviainen T;Winqvist R;Kadhim M;Launonen V;Lindholm C
采用染色体畸变(CA)分析方法，对ATM杂合子携带者和A-T患者(双等位ATM突变)淋巴母细胞系(LCLS)进行了低剂量和高剂量X射线照射敏感性的研究。通过应用共培养系统，可以在相同的实验环境中研究直接照射的细胞和介质介导的旁观者效应，从而检验了对急性照射的靶向和非靶向反应。对于ATM突变携带者LCL，在0.01Gy或0.1Gy剂量下未观察到辐射过敏迹象。A-T患者细胞也没有表现出低剂量反应。ATM突变携带者和A-T LCLS的不稳定CA产量在1Gy1和2Gy时均显著增加，且A-T细胞表现出更明显的剂量依赖性。在照射后的A-T细胞中，染色体和染色单体类型的畸变率均增加，而在ATM载体细胞中，只有不稳定的染色体畸变率高于野生型细胞系。在所应用的任何细胞系或剂量中都没有显示出旁观者效应。检测到A-T细胞系的典型特征，即CA的高基线频率随着剂量的增加而增加。此外，还观察到细胞活力的剂量依赖性损失。总之，CA分析没有证明≤突变携带者细胞或A-T患者细胞对低剂量(ATM100mGY)的放射敏感性。然而，这两种细胞系在高剂量暴露时都表现出更高的放射敏感性。
Radiation sensitivity at low and high dose exposure to X-rays was investigated by means of chromosomal aberration (CA) analysis in heterozygous ATM mutation carrier and A-T patient (biallelic ATM mutation) lymphoblastoid cell lines (LCLs). Targeted and non-targeted responses to acutely delivered irradiation were examined by applying a co-culture system that enables study of both directly irradiated cells and medium-mediated bystander effects in the same experimental setting. No indication of radiation hypersensitivity was observed at doses of 0.01 Gy or 0.1 Gy for the ATM mutation carrier LCL. The A-T patient cells also did not show low-dose response. There was significant increase in unstable CA yields for both ATM mutation carrier and A-T LCLs at 1 and 2 Gy, the A-T cells displaying more distinct dose dependency. Both chromosome and chromatid type aberrations were induced at an increased rate in the irradiated A-T cells, whereas for ATM carrier cells, only unstable chromosomal aberrations were increased above the level observed in the wild type cell line. No bystander effect could be demonstrated in any of the cell lines or doses applied. Characteristics typical for the A-T cell line were detected, i.e., high baseline frequency of CA that increased with dose. In addition, dose-dependent loss of cell viability was observed. In conclusion, CA analysis did not demonstrate low-dose (≤100 mGy) radiosensitivity in ATM mutation carrier cells or A-T patient cells. However, both cell lines showed increased radiosensitivity at high dose exposure.
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影响因子：
3.4
作者：
George, Kerry A.;Hada, Megumi;Cucinotta, Francis A.
通讯作者：
Cucinotta, Francis A.
影响因子：
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作者：
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影响因子：
3.4
作者：
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通讯作者：
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影响因子：
2.3
作者：
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通讯作者：
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影响因子：
4.7
作者：
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通讯作者：
Winqvist, Robert