Radiation-induced instability and its relation to radiation carcinogenesis.
Radiation-induced instability and its relation to radiation carcinogenesis.
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DOI：
10.1080/095530098141023
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发表时间：
1998-12
影响因子：
2.6
通讯作者：
R. Ullrich;Brian Ponnaiya
中科院分区：
文献类型：
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作者：
R. Ullrich;Brian Ponnaiya
目的先前提出了一种模型，该模型将辐射引起的遗传不稳定性识别为导致辐射诱发癌症的多步骤序列中最早的细胞事件。本文讨论了正在进行的实验，这些实验旨在测试该模型及其在小鼠乳腺上皮细胞中的预测。结果 提出的几条证据似乎支持该模型：首先，在改变的生长变异体中，照射后 p53 发生延迟突变；其次，乳腺上皮细胞辐射后诱导不稳定和转化的频率很高；最后，证明对诱导细胞遗传学不稳定的易感性是一种遗传性状，与对转化和辐射诱发的乳腺癌的易感性相关。对转化和乳腺癌发展具有抵抗力的小鼠也能抵抗辐射后不稳定的发展。相比之下，对转化和癌症敏感的小鼠也对细胞遗传学不稳定的发展敏感。结论 该实验室和上述研究的数据表明，辐射引起的不稳定性作为与致癌过程启动相关的关键早期事件，具有特定的、也许是独特的作用。
PURPOSE A model that identifies radiation-induced genetic instability as the earliest cellular event in the multi-step sequence leading to radiation-induced cancer was previously proposed. In this paper ongoing experiments are discussed which are designed to test this model and its predictions in mouse mammary epithelial cells. RESULTS Several lines of evidence are presented that appear to support this model: first, the development of delayed mutations in p53 following irradiation in altered growth variants; secondly, the high frequencies for the induction of both instability and transformation following irradiation in mammary epithelial cells; and finally, the demonstration that susceptibility to the induction of cytogenetic instability is a heritable trait that correlates with susceptibility to transformation and radiation-induced mammary cancer. Mice resistant to transformation and mammary cancer development are also resistant to the development of instability after irradiation. In contrast, mice sensitive to transformation and cancer are also sensitive to the development of cytogenetic instability. CONCLUSIONS Data from this laboratory and from the studies cited above suggest a specific, and perhaps unique, role for radiation-induced instability as a critical early event associated with initiation of the carcinogenic process.