Christ's College, University of Cambridge, Cambridge, UK.
Oncogene. 2008 Dec;27 Suppl 2:S9-18. doi: 10.1038/onc.2009.349.
Radiation is a carcinogen, interacting with DNA to produce a range of mutations. Irradiated cells also show genomic instability, as do adjacent non-irradiated cells (the bystander effect); the importance to carcinogenesis remains to be established. Current knowledge of radiation effects is largely dependent on evidence from exposure to atomic bomb whole body radiation, leading to increases in a wide range of malignancies. In contrast, millions of people were exposed to radioactive isotopes in the fallout from the Chernobyl accident, within the first 20 years there was a large increase in thyroid carcinoma incidence and a possible radiation-related increase in breast cancer, but as yet there is no general increase in malignancies. The increase in thyroid carcinoma, attributable to the very large amounts of iodine 131 released, was first noticed in children with a strong relationship between young age at exposure and risk of developing papillary thyroid carcinoma (PTC). The extent of the increase, the reasons for the relationship to age at exposure, the reduction in attributable fraction with increasing latency and the role of environmental factors are discussed. The large number of radiation-induced PTCs has allowed new observations. The subtype and molecular findings change with latency; most early cases were solid PTCs with RET-PTC3 rearrangements, later cases were classical PTCs with RET-PTC1 rearrangements. Small numbers of many other RET rearrangements have occurred in 'Chernobyl' PTCs, and also rearrangement of BRAF. Five of the N-terminal genes found in papillary carcinoma rearrangements are also involved in rearrangements in hematological malignancies; three are putative tumor suppressor genes, and two are further genes fused to RET in PTCs. Radiation causes double-strand breaks; the rearrangements common in these radiation-induced tumors reflect their etiology. It is suggested that oncogenic rearrangements may commonly involve both a tumor-suppressor gene (or a DNA repair gene) as well as an oncogene. Involvement of two relevant genes would give a greater chance of progression and a shorter latency than a single-gene mutation. More information is needed on germline mutations conferring susceptibility to radiation-induced PTCs, particularly DNA repair genes. The radiation exposure to the fallout after Chernobyl was very different from the whole body radiation after the atomic bombs. The type and molecular pathology of the thyroid tumors is changing with increasing latency, long latency tumors in other organs could occur in the future. A comprehensive follow up must continue for the lifetime of those exposed.
辐射是一种致癌物质，与 DNA 相互作用会产生多种突变。受照射的细胞还表现出基因组不稳定性，相邻的未受照射细胞也是如此（旁观者效应）；其对致癌作用的重要性仍有待确定。目前对辐射效应的认识在很大程度上依赖于原子弹全身照射暴露的证据，这导致了多种恶性肿瘤的发生率增加。相比之下，有数百万人在切尔诺贝利事故的放射性沉降物中暴露于放射性同位素，在前 20 年中，甲状腺癌的发病率大幅上升，乳腺癌的发病率可能与辐射有关，但目前尚无恶性肿瘤总体增加的趋势。归因于大量释放的碘 131，甲状腺癌的发病率增加首先在儿童中被发现，并且在暴露年龄与发生乳头状甲状腺癌（PTC）的风险之间存在很强的关系。讨论了增加的程度、与暴露年龄的关系的原因、归因分数随潜伏期的增加而减少以及环境因素的作用。大量的辐射诱导的 PTC 使得新的观察成为可能。亚型和分子发现随潜伏期而变化；大多数早期病例为实性 PTC，伴有 RET-PTC3 重排，后来的病例为经典的 PTC，伴有 RET-PTC1 重排。在“切尔诺贝利”PTC 中还发生了少量其他 RET 重排，以及 BRAF 重排。在甲状腺癌重排中发现的 N 端基因中的 5 个也涉及血液恶性肿瘤中的重排；其中 3 个是推定的肿瘤抑制基因，另外 2 个是在 PTC 中与 RET 融合的基因。辐射会导致双链断裂；这些辐射诱导的肿瘤中常见的重排反映了它们的病因。因此，致癌重排可能通常涉及肿瘤抑制基因（或 DNA 修复基因）和癌基因。与两个相关基因的涉及会比单个基因突变更有可能进展和潜伏期更短。需要更多关于赋予对辐射诱导的 PTC 易感性的种系突变的信息，特别是 DNA 修复基因。切尔诺贝利事故放射性沉降物的辐射暴露与原子弹后的全身辐射非常不同。甲状腺肿瘤的类型和分子病理学随着潜伏期的增加而发生变化，未来其他器官的潜伏期较长的肿瘤可能会发生。对于受暴露的人，必须在其整个生命过程中进行全面的随访。
