Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108, USA.
Dose Response. 2006 May 22;3(4):547-67. doi: 10.2203/dose-response.003.04.009.
New research data for low-dose, low-linear energy transfer (LET) radiation-induced, stochastic effects (mutations and neoplastic transformations) are modeled using the recently published NEOTRANS(3) model. The model incorporates a protective, stochastic threshold (StoThresh) at low doses for activating cooperative protective processes considered to include presumptive p53-dependent, high-fidelity repair of nuclear DNA damage in competition with presumptive p53-dependent apoptosis and a novel presumptive p53-independent protective apoptosis mediated (PAM) process which selectively removes genomically compromised cells (mutants, neoplastic transformants, micronucleated cells, etc.). The protective StoThresh are considered to fall in a relatively narrow low-dose zone (Transition Zone A). Below Transition Zone A is the ultra-low-dose region where it is assumed that only low-fidelity DNA repair is activated along with presumably apoptosis. For this zone there is evidence for an increase in mutations with increases in dose. Just above Transition Zone A, a Zone of Maximal Protection (suppression of stochastic effects) arises and is attributed to maximal cooperation of high-fidelity, DNA repair/apoptosis and the PAM process. The width of the Zone of Maximal Protection depends on low-LET radiation dose rate and appears to depend on photon radiation energy. Just above the Zone of Maximal Protection is Transition Zone B, where deleterious StoThresh for preventing the PAM process fall. Just above Transition Zone B is a zone of moderate doses where complete inhibition of the PAM process appears to occur. However, for both Transition Zone B and the zone of complete inhibition of the PAM process, high-fidelity DNA repair/apoptosis are presumed to still operate. The indicated protective and deleterious StoThresh lead to nonlinear, hormetic-type dose-response relationships for low-LET radiation-induced mutations, neoplastic transformation and, presumably, also for cancer.
新的低剂量、低线性能量转移（LET）辐射诱导的随机性效应（突变和肿瘤转化）研究数据使用最近发表的 NEOTRANS(3)模型进行建模。该模型在低剂量下包含一个保护性的随机性阈值（StoThresh），用于激活协同保护过程，这些过程被认为包括假定的 p53 依赖性、核 DNA 损伤的高保真修复，与假定的 p53 依赖性细胞凋亡竞争，以及一种新的假定的 p53 独立的保护性细胞凋亡介导（PAM）过程，该过程选择性地去除基因组受损的细胞（突变体、肿瘤转化体、微核细胞等）。保护性 StoThresh 被认为处于相对较窄的低剂量区（过渡区 A）。过渡区 A 以下是超低剂量区，在该区域中仅假定激活低保真 DNA 修复以及可能的细胞凋亡。对于该区域，有证据表明随着剂量的增加，突变增加。就在过渡区 A 上方，出现了最大保护区（抑制随机性效应），这归因于高保真、DNA 修复/细胞凋亡和 PAM 过程的最大合作。最大保护区的宽度取决于低 LET 辐射剂量率，并且似乎取决于光子辐射能量。就在最大保护区上方是过渡区 B，其中阻止 PAM 过程的有害 StoThresh 下降。就在过渡区 B 上方是一个中等剂量区，其中 PAM 过程似乎完全被抑制。然而，对于过渡区 B 和 PAM 过程完全抑制的区域，高保真 DNA 修复/细胞凋亡被假定仍在起作用。指示的保护性和有害性 StoThresh 导致低 LET 辐射诱导的突变、肿瘤转化以及假定的癌症的非线性、激素样剂量反应关系。
