Hamada Nobuyuki, Matsuya Yusuke, Zablotska Lydia B, Little Mark P
Biology and Environmental Chemistry Division, Sustainable System Research Laboratory, Central Research Institute of Electric Power Industry (CRIEPI), Chiba 270-1194, Japan.
Faculty of Health Sciences, Hokkaido University, Hokkaido 060-0812, Japan; Research Group for Radiation Transport Analysis, Nuclear Science and Engineering Center, Japan Atomic Energy Agency (JAEA), Ibaraki 319-1195, Japan.
Mutat Res Rev Mutat Res. 2025 Jan-Jun;795:108530. doi: 10.1016/j.mrrev.2025.108530. Epub 2025 Jan 14.
Biological effects of ionizing radiation vary with radiation quality, which is often expressed as the amount of energy deposited per unit length, i.e., linear energy transfer (LET). For acute irradiation, high-LET radiation generally produces greater biological effects than low-LET radiation, but little knowledge exists as to how dose protraction modifies effects. In this regard, inverse dose protraction effects (IDPEs) are phenomena in which dose protraction enhances effects, contrasting with sparing dose protraction effects in which dose protraction reduces effects. Here, we review the current knowledge on IDPEs of high-LET radiation. To the best of our knowledge, since 1967, 80 biology or epidemiology papers have reported IDPEs following external or internal high-LET irradiation with neutrons, deuterons, α-particles, light ions, or heavy ions. IDPEs of high-LET radiation have been described for biochemical changes in cell-free macromolecules, neoplastic transformation, cell death, DNA damage responses and gene expression changes in mammalian cell cultures of human or rodent origin, gene mutations, cytogenetic changes, cancer, non-cancer effects (e.g., testicular effects, cataracts, cardiovascular diseases) and life shortening in non-human mammals (rodents and dogs), and induction of lung cancer and bone tumors in humans. For external irradiation of mammalian cells in vitro and mammals in vivo, IDPEs of low- and high-LET radiation have been reported for radiation doses spanning in excess of three or four orders of magnitude in slightly different ranges, and for radiation dose rates both spanning over six orders of magnitude in different ranges. IDPEs of high-LET radiation in humans have been reported following internal exposure, but not external exposure. Manifestations and mechanisms of IDPEs of high-LET radiation are far less understood than those of low-LET radiation, warranting further studies that will be pivotal to assess the implications for radiation protection.
电离辐射的生物学效应随辐射品质而异,辐射品质通常表示为单位长度沉积的能量,即传能线密度(LET)。对于急性照射,高LET辐射通常比低LET辐射产生更大的生物学效应,但关于剂量延长如何改变效应的了解甚少。在这方面,逆剂量延长效应(IDPE)是指剂量延长增强效应的现象,这与剂量延长减少效应的剂量节省效应形成对比。在此,我们综述了关于高LET辐射IDPE的现有知识。据我们所知,自1967年以来,有80篇生物学或流行病学论文报道了在受到中子、氘核、α粒子、轻离子或重离子的外部或内部高LET照射后出现的IDPE。高LET辐射的IDPE已在无细胞大分子的生化变化、肿瘤转化、细胞死亡、DNA损伤反应以及人源或啮齿动物源哺乳动物细胞培养中的基因表达变化、基因突变、细胞遗传学变化、癌症、非癌症效应(如睾丸效应、白内障、心血管疾病)以及非人类哺乳动物(啮齿动物和狗)的寿命缩短,以及人类肺癌和骨肿瘤的诱导等方面得到描述。对于体外哺乳动物细胞和体内哺乳动物的外部照射,低LET和高LET辐射的IDPE已在略不同范围内超过三或四个数量级的辐射剂量以及不同范围内超过六个数量级的辐射剂量率下得到报道。高LET辐射在人体内的IDPE已在内部暴露后被报道,但外部暴露后未被报道。高LET辐射IDPE的表现和机制远不如低LET辐射那样为人所理解,因此有必要进行进一步研究,这对于评估其对辐射防护的影响至关重要。