Rivina Leena, Davoren Michael J, Schiestl Robert H
Department of Environmental Health Sciences.
Department of Environmental Health Sciences,
Mutagenesis. 2016 Sep;31(5):491-509. doi: 10.1093/mutage/gew019. Epub 2016 May 21.
Potential ionising radiation exposure scenarios are varied, but all bring risks beyond the simple issues of short-term survival. Whether accidentally exposed to a single, whole-body dose in an act of terrorism or purposefully exposed to fractionated doses as part of a therapeutic regimen, radiation exposure carries the consequence of elevated cancer risk. The long-term impact of both intentional and unintentional exposure could potentially be mitigated by treatments specifically developed to limit the mutations and precancerous replication that ensue in the wake of irradiation The development of such agents would undoubtedly require a substantial degree of in vitro testing, but in order to accurately recapitulate the complex process of radiation-induced carcinogenesis, well-understood animal models are necessary. Inbred strains of the laboratory mouse, Mus musculus, present the most logical choice due to the high number of molecular and physiological similarities they share with humans. Their small size, high rate of breeding and fully sequenced genome further increase its value for use in cancer research. This chapter will review relevant m. musculus inbred and F1 hybrid animals of radiation-induced myeloid leukemia, thymic lymphoma, breast and lung cancers. Method of cancer induction and associated molecular pathologies will also be described for each model.
潜在的电离辐射暴露情况多种多样,但所有这些情况带来的风险都超出了短期生存的简单问题。无论是在恐怖袭击中意外受到单次全身剂量照射,还是作为治疗方案的一部分有意接受分次剂量照射,辐射暴露都会带来癌症风险升高的后果。有意和无意暴露的长期影响都有可能通过专门开发的治疗方法来减轻,这些治疗方法旨在限制辐射后发生的突变和癌前复制。开发此类药物无疑需要进行大量的体外测试,但为了准确重现辐射诱导致癌的复杂过程,了解透彻的动物模型是必要的。实验室小鼠(小家鼠)的近交系是最合理的选择,因为它们与人类在分子和生理方面有大量相似之处。它们体型小、繁殖率高且基因组已完全测序,这进一步增加了其在癌症研究中的价值。本章将综述小家鼠近交系和F1杂交动物辐射诱导的髓系白血病、胸腺淋巴瘤、乳腺癌和肺癌。还将针对每个模型描述癌症诱导方法及相关分子病理学。