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线性无阈模型(LNT)不能为癌症诱发提供放射生物学数据支持。

The LNT model for cancer induction is not supported by radiobiological data.

机构信息

2900 Vista Del Rey NE, Unit 22D, Albuquerque, NM, USA.

Northern Ontario School of Medicine, Laurentian University, 935 Ramsey Lake Rd, Sudbury, ON, P3E 2C6, Canada.

出版信息

Chem Biol Interact. 2019 Mar 1;301:34-53. doi: 10.1016/j.cbi.2019.01.013. Epub 2019 Feb 11.

Abstract

The hallmarks of cancer have been the focus of much research and have influenced the development of risk models for radiation-induced cancer. However, natural defenses against cancer, which constitute the hallmarks of cancer prevention, have largely been neglected in developing cancer risk models. These natural defenses are enhanced by low doses and dose rates of ionizing radiation, which has aided in the continuation of human life over many generations. Our natural defenses operate at the molecular, cellular, tissue, and whole-body levels and include epigenetically regulated (epiregulated) DNA damage repair and antioxidant production, selective p53-independent apoptosis of aberrant cells (e.g. neoplastically transformed and tumor cells), suppression of cancer-promoting inflammation, and anticancer immunity (both innate and adaptive components). This publication reviews the scientific bases for the indicated cancer-preventing natural defenses and evaluates their implication for assessing cancer risk after exposure to low radiation doses and dose rates. Based on the extensive radiobiological evidence reviewed, it is concluded that the linear-no-threshold (LNT) model (which ignores natural defenses against cancer), as it relates to cancer risk from ionizing radiation, is highly implausible. Plausible models include dose-threshold and hormetic models. More research is needed to establish when a given model (threshold, hormetic, or other) applies to a given low-dose-radiation exposure scenario.

摘要

癌症的特征一直是许多研究的焦点,并影响了辐射诱导癌症风险模型的发展。然而,在开发癌症风险模型时,构成癌症预防特征的天然防御机制在很大程度上被忽视了。这些天然防御机制在低剂量和低剂量率的电离辐射下得到增强,这有助于人类在许多代中延续生命。我们的天然防御机制在分子、细胞、组织和全身水平上运作,包括受表观遗传调控的 (epiregulated) DNA 损伤修复和抗氧化剂的产生、异常细胞(如癌变和肿瘤细胞)的选择性不依赖 p53 的凋亡、抑制促进癌症的炎症以及抗癌免疫(包括先天和适应性成分)。本出版物回顾了表明的癌症预防天然防御的科学基础,并评估了它们对评估低剂量和低剂量率辐射暴露后癌症风险的意义。基于所审查的广泛放射生物学证据,得出的结论是,线性无阈值 (LNT) 模型(忽略了对癌症的天然防御)与电离辐射致癌风险高度不符。合理的模型包括剂量阈值和适应原模型。需要进一步研究以确定给定模型(阈值、适应原或其他模型)适用于给定的低剂量辐射暴露情况。

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