{"title":"辐射对人类的跨代影响难以检测的三大原因。","authors":"Nori Nakamura, Noriaki Yoshida, Tatsuya Suwa","doi":"10.1080/09553002.2023.2187478","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Ionizing radiation can induce mutations in germ cells in various organisms, including fruit flies and mice. However, currently, there is no clear evidence for the transgenerational effects of radiation in humans. This review is an effort to identify possible reasons for the lack of such observations.</p><p><strong>Methods: </strong>Literature search and narrative review.</p><p><strong>Results: </strong>1) In both mice and humans, resting oocytes locate primarily in the cortical region of the ovary where the number of blood vessels is very low especially when young and extra-cellular material is rich, and this region is consequently hypoxic, which probably leads to immature oocytes being resistant to the cell killing and mutagenic effects of radiation. 2) In studies of spermatogonia, the mouse genes used for specific locus test (SLT) studies, which include coat color genes, were hypermutable when compared to many other genes. Recent studies which examined over 1000 segments of genomic DNA indicate that the induction rate of deletion mutation per segment was on the order of 10<sup>-6</sup> per Gy, which is one order of magnitude lower than that obtained from the SLT data. Therefore, it appears possible that detecting any transgenerational effects of radiation following human male exposures will be difficult due to a lack of mutable marker genes. 3) Fetal malformations were examined in studies in humans, but the genetic component in such malformations is low, and abnormal fetuses are prone to undergo miscarriage which does not occur in mice, and which leads to difficulties in detecting transgenerational effects.</p><p><strong>Conclusion: </strong>The lack of clear evidence for radiation effects in humans probably does not result from any problem in the methodologies used but may be due largely to biological properties. Currently, whole genome sequencing studies of exposed parents and offspring are planned, but ethical guidelines need to be followed to avoid discrimination, which had once happened to the atomic bomb survivors.</p>","PeriodicalId":14261,"journal":{"name":"International Journal of Radiation Biology","volume":" ","pages":"1297-1311"},"PeriodicalIF":2.1000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Three major reasons why transgenerational effects of radiation are difficult to detect in humans.\",\"authors\":\"Nori Nakamura, Noriaki Yoshida, Tatsuya Suwa\",\"doi\":\"10.1080/09553002.2023.2187478\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Ionizing radiation can induce mutations in germ cells in various organisms, including fruit flies and mice. However, currently, there is no clear evidence for the transgenerational effects of radiation in humans. This review is an effort to identify possible reasons for the lack of such observations.</p><p><strong>Methods: </strong>Literature search and narrative review.</p><p><strong>Results: </strong>1) In both mice and humans, resting oocytes locate primarily in the cortical region of the ovary where the number of blood vessels is very low especially when young and extra-cellular material is rich, and this region is consequently hypoxic, which probably leads to immature oocytes being resistant to the cell killing and mutagenic effects of radiation. 2) In studies of spermatogonia, the mouse genes used for specific locus test (SLT) studies, which include coat color genes, were hypermutable when compared to many other genes. Recent studies which examined over 1000 segments of genomic DNA indicate that the induction rate of deletion mutation per segment was on the order of 10<sup>-6</sup> per Gy, which is one order of magnitude lower than that obtained from the SLT data. Therefore, it appears possible that detecting any transgenerational effects of radiation following human male exposures will be difficult due to a lack of mutable marker genes. 3) Fetal malformations were examined in studies in humans, but the genetic component in such malformations is low, and abnormal fetuses are prone to undergo miscarriage which does not occur in mice, and which leads to difficulties in detecting transgenerational effects.</p><p><strong>Conclusion: </strong>The lack of clear evidence for radiation effects in humans probably does not result from any problem in the methodologies used but may be due largely to biological properties. Currently, whole genome sequencing studies of exposed parents and offspring are planned, but ethical guidelines need to be followed to avoid discrimination, which had once happened to the atomic bomb survivors.</p>\",\"PeriodicalId\":14261,\"journal\":{\"name\":\"International Journal of Radiation Biology\",\"volume\":\" \",\"pages\":\"1297-1311\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Radiation Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/09553002.2023.2187478\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/3/15 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Radiation Biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/09553002.2023.2187478","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/3/15 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的：电离辐射可诱导果蝇和小鼠等多种生物的生殖细胞发生突变。然而，目前还没有明确的证据表明辐射会对人类产生跨代影响。本综述旨在找出缺乏此类观察结果的可能原因：方法：文献检索和叙述性综述：1）在小鼠和人类中，静止卵母细胞主要位于卵巢皮质区，该区域的血管数量很少，尤其是在幼年时期，细胞外物质丰富，因此该区域缺氧，这可能导致未成熟卵母细胞对辐射的细胞杀伤和致突变效应具有抵抗力。2）在对精原细胞的研究中，用于特异位点测试（SLT）研究的小鼠基因（包括被毛颜色基因）与许多其他基因相比具有高突变性。最近对超过 1000 个基因组 DNA 片段进行的研究表明，每个片段的缺失突变诱导率约为 10-6 per Gy，比 SLT 数据低一个数量级。因此，由于缺乏可突变的标记基因，似乎很难检测到人类男性受辐射后产生的任何跨代影响。3）在人类研究中对胎儿畸形进行了检测，但这种畸形的遗传成分较低，而且异常胎儿容易流产，而小鼠不会发生这种情况，这导致难以检测到跨代效应：结论：缺乏明确证据证明辐射对人类的影响可能并不是因为所使用的方法有问题，而可能主要是由于生物特性造成的。目前，计划对受辐射的父母和后代进行全基因组测序研究，但需要遵守伦理准则，以避免歧视，原子弹爆炸幸存者就曾遭受过歧视。
Three major reasons why transgenerational effects of radiation are difficult to detect in humans.
Purpose: Ionizing radiation can induce mutations in germ cells in various organisms, including fruit flies and mice. However, currently, there is no clear evidence for the transgenerational effects of radiation in humans. This review is an effort to identify possible reasons for the lack of such observations.
Methods: Literature search and narrative review.
Results: 1) In both mice and humans, resting oocytes locate primarily in the cortical region of the ovary where the number of blood vessels is very low especially when young and extra-cellular material is rich, and this region is consequently hypoxic, which probably leads to immature oocytes being resistant to the cell killing and mutagenic effects of radiation. 2) In studies of spermatogonia, the mouse genes used for specific locus test (SLT) studies, which include coat color genes, were hypermutable when compared to many other genes. Recent studies which examined over 1000 segments of genomic DNA indicate that the induction rate of deletion mutation per segment was on the order of 10-6 per Gy, which is one order of magnitude lower than that obtained from the SLT data. Therefore, it appears possible that detecting any transgenerational effects of radiation following human male exposures will be difficult due to a lack of mutable marker genes. 3) Fetal malformations were examined in studies in humans, but the genetic component in such malformations is low, and abnormal fetuses are prone to undergo miscarriage which does not occur in mice, and which leads to difficulties in detecting transgenerational effects.
Conclusion: The lack of clear evidence for radiation effects in humans probably does not result from any problem in the methodologies used but may be due largely to biological properties. Currently, whole genome sequencing studies of exposed parents and offspring are planned, but ethical guidelines need to be followed to avoid discrimination, which had once happened to the atomic bomb survivors.
期刊介绍：
The International Journal of Radiation Biology publishes original papers, reviews, current topic articles, technical notes/reports, and meeting reports on the effects of ionizing, UV and visible radiation, accelerated particles, electromagnetic fields, ultrasound, heat and related modalities. The focus is on the biological effects of such radiations: from radiation chemistry to the spectrum of responses of living organisms and underlying mechanisms, including genetic abnormalities, repair phenomena, cell death, dose modifying agents and tissue responses. Application of basic studies to medical uses of radiation extends the coverage to practical problems such as physical and chemical adjuvants which improve the effectiveness of radiation in cancer therapy. Assessment of the hazards of low doses of radiation is also considered.
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