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Low Dose Diagnostic Radiation Does Not Increase Cancer Risk in Cancer Prone Mice

机译:低剂量诊断放射线不会增加易患癌症小鼠的癌症风险

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The increased exposure of patients to low dose diagnostic ionizing radiation has created concern that these procedures will result in greater risk of carcinogenesis. However, there is substantial evidence that shows in many cases that low dose exposure has the opposite effect. We have investigated whether CT scans can modify mechanisms associated with carcinogenesis in cancer-prone mice. Cancer was induced in Trp53+/- mice with an acute high dose whole-body 4 Gy y-radiation exposure. Four weeks following the cancer-inducing dose, weekly whole-body CT scans (10 mGy/scan, 75 kVp X-rays) were given for ten consecutive weeks adding an additional radiation burden of 0.1 Gy. Short-term biological responses and subsequent lifetime cancer risk were investigated. Five days following the last CT scan, there were no detectable differences in the spontaneous levels of DNA damage in blood cells (reticulocytes). hi fact, CT scanned mice had significantly lower constitutive levels of oxidative DNA damage and cell death (apoptosis), compared to non-CT scanned mice. This shows that multiple low dose radiation exposures modified the radioresponse and indicates protective processes were induced in mice, hi mice treated with the multiple CT scans following the high cancer-inducing 4 Gy dose, tumour latency was increased, significantly prolonging lifespan. We conclude that repeated CT scans can reduce the cancer risk of a prior high-dose radiation exposure, and delay the progression of specific types of radiation-induced cancers in Trp53+/-mice. This research shows for the first time that low dose exposure long after cancer initiation events alter risk and reduce cancer morbidity. Cancer induction following low doses does not follow a linear non-threshold model of risk and this model should not be used to extrapolate risk to humans following low dose exposure to ionizing radiation.
机译:患者越来越多地暴露于低剂量诊断电离辐射中,引起人们的担忧,即这些程序将导致更大的致癌风险。但是,有充分的证据表明,在许多情况下,低剂量暴露具有相反的作用。我们已经研究了CT扫描是否可以改变易患癌症小鼠中与癌变相关的机制。 Trp53 +/-小鼠在急性高剂量全身4 Gy y射线照射下诱发癌症。致癌剂量四周后,连续十周每周进行全身CT扫描(10 mGy /扫描,75 kVp X射线),增加了0.1 Gy的额外放射负荷。研究了短期生物学反应和随后的终生癌症风险。在最后一次CT扫描后五天,血细胞(网织红细胞)的自发性DNA损伤水平没有可检测到的差异。实际上,与非CT扫描的小鼠相比,CT扫描的小鼠的氧化性DNA损伤和细胞死亡(细胞凋亡)的组成水平明显降低。这表明多次低剂量辐射暴露改变了放射反应,并表明在小鼠中诱导了保护过程。在高诱导癌性的4 Gy剂量后用多次CT扫描治疗的小鼠中,肿瘤潜伏期增加,显着延长了寿命。我们得出的结论是,反复进行CT扫描可以降低以前的大剂量放射线照射所致的癌症风险,并延迟Trp53 +/-小鼠中特定类型的放射线诱发的癌症的进展。这项研究首次表明,在癌症引发事件发生很长时间之后,低剂量暴露会改变风险并降低癌症发病率。低剂量后的癌症诱导并未遵循线性非阈值风险模型,并且该模型不应用于将低剂量暴露于电离辐射后对人类的风险外推。

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