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Low-Dose Cancer Risk Modeling Must Recognize Up-Regulation of Protection

机译:低剂量癌症风险建模必须认识到保护的上调

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Ionizing radiation primarily perturbs the basic molecular level proportional to dose, with potential damage propagation to higher levels: cells, tissues, organs, and whole body. There are three types of defenses against damage propagation. These operate deterministically and below a certain impact threshold there is no propagation. Physical-static defenses precede metabolic-dynamic defenses acting immediately: scavenging of toxins; - molecular repair, especially of DNA; - removal of damaged cells either by apoptosis, necrosis, phagocytosis, cell differentiation-senescence, or by immune responses, - followed by replacement of lost elements. Another metabolic-dynamic defense arises delayed by up-regulating immediately operating defense mechanisms. Some of these adaptive protections may last beyond a year and all create temporary protection against renewed potentially toxic impacts also from non-radiogenic endogenous sources. Adaptive protections have a maximum after single tissue absorbed doses around 100 to 200 mSv and disappear with higher doses. Low dose rates initiate maximum protection likely at lower cell doses delivered repetitively at certain time intervals. Adaptive protection preventing only about 2 – 3 % of endogenous life-time cancer risk would fully balance a calculated induced cancer risk at about 100 mSv, in agreement with epidemiological data and concordant with an hormetic effect. Low-dose-risk modeling must recognize up-regulation of protection.
机译:电离辐射主要扰动与剂量成比例的基本分子水平,并且潜在的损害传播到更高的水平:细胞,组织,器官和全身。防御损害传播的防御有三种类型。它们确定性地运行,并且在一定的影响阈值以下,没有传播。静态静态防御先于新陈代谢动态防御立即采取行动:清除毒素; -分子修复,尤其是DNA修复; -通过凋亡,坏死,吞噬作用,细胞分化-衰老或通过免疫反应去除受损细胞-随后替换丢失的元件。另一种代谢动力学防御由于上调立即运行的防御机制而延迟出现。这些适应性保护措施中的某些可能会持续一年以上,并且都可以针对非放射源性内源性来源产生的新的潜在毒性影响提供临时保护。在单个组织吸收约100至200 mSv的剂量后,适应性保护作用最大,而在更高剂量下消失。低剂量率可能会在一定的时间间隔内反复传递较低的细胞剂量时启动最大保护。与流行病学数据相一致并与止痛效果相一致,仅能预防约2 – 3%的内源性终生癌症风险的自适应保护将完全平衡计算出的约100 mSv的诱发癌症风险。低剂量风险建模必须认识到保护的上调。

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