Department of Radiation Oncology, Wake Forest School of Medicine, Wake Forest University, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA.
Radiat Res. 2011 Dec;176(6):842-8. doi: 10.1667/rr2649.1. Epub 2011 Sep 30.
A >20-fold increase in X-ray computed tomography (CT) use during the last 30 years has caused considerable concern because of the potential carcinogenic risk from these CT exposures. Estimating the carcinogenic risk from high-energy, single high-dose exposures obtained from atomic bomb survivors and extrapolating these data to multiple low-energy, low-dose CT exposures using the Linear No-Threshold (LNT) model may not give an accurate assessment of actual cancer risk. Recently, the National Lung Cancer Screening Trial (NLST) reported that annual CT scans of current and former heavy smokers reduced lung cancer mortality by 20%, highlighting the need to better define the carcinogenic risk associated with these annual CT screening exposures. In this study, we used the bitransgenic CCSP-rtTA/Ki-ras mouse model that conditionally expresses the human mutant Ki-ras(G12C) gene in a doxycycline-inducible and lung-specific manner to measure the carcinogenic risk of exposure to multiple whole-body CT doses that approximate the annual NLST screening protocol. Irradiated mice expressing the Ki-ras(G12C) gene in their lungs had a significant (P = 0.01) 43% increase in the number of tumors/mouse (24.1 ± 1.9) compared to unirradiated mice (16.8 ± 1.3). Irradiated females had significantly (P < 0.005) more excess tumors than irradiated males. No tumor size difference or dose response was observed over the total dose range of 80-160 mGy for either sex. Irradiated bitransgenic mice that did not express the Ki-ras(G12C) gene had a low tumor incidence (≤ 0.1/mouse) that was not affected by exposure to CT radiation. These results suggest that (i) estimating the carcinogenic risk of multiple CT exposures from high-dose carcinogenesis data using the LNT model may be inappropriate for current and former smokers and (ii) any increased carcinogenic risk after exposure to fractionated low-dose CT-radiation may be restricted to only those individuals expressing cancer susceptibility genes in their tissues at the time of exposure.
在过去的 30 年中，X 射线计算机断层扫描（CT）的使用增加了 20 多倍，这引起了相当大的关注，因为这些 CT 暴露存在潜在的致癌风险。从原子弹幸存者的高能单次高剂量暴露中估计致癌风险，并使用线性无阈值（LNT）模型将这些数据外推到多次低能低剂量 CT 暴露，可能无法准确评估实际癌症风险。最近，国家肺癌筛查试验（NLST）报告称，目前和以前的重度吸烟者每年进行 CT 扫描可降低 20%的肺癌死亡率，这凸显了需要更好地定义与这些年度 CT 筛查暴露相关的致癌风险。在这项研究中，我们使用了双转基因 CCSP-rtTA/Ki-ras 小鼠模型，该模型以四环素诱导和肺特异性的方式条件性表达人类突变的 Ki-ras(G12C)基因，以测量接近年度 NLST 筛查方案的多次全身 CT 剂量暴露的致癌风险。在肺部表达 Ki-ras(G12C)基因的照射小鼠中，肿瘤/小鼠的数量显著增加（P = 0.01），为 43%（24.1 ± 1.9），而未照射的小鼠为 16.8 ± 1.3）。照射的雌性比照射的雄性有显著更多的多余肿瘤（P < 0.005）。在 80-160 mGy 的总剂量范围内，无论是男性还是女性，都没有观察到肿瘤大小差异或剂量反应。未表达 Ki-ras(G12C)基因的照射双转基因小鼠的肿瘤发生率较低（≤0.1/小鼠），不受 CT 辐射暴露的影响。这些结果表明，（i）使用 LNT 模型从高剂量致癌数据估计多次 CT 暴露的致癌风险对于当前和以前的吸烟者可能不合适，（ii）在暴露于分割低剂量 CT 辐射后，任何增加的致癌风险可能仅限于在暴露时其组织中表达癌症易感性基因的个体。
