Janowski M, Cox R, Strauss P G
SCK/CEN, Department of Radioprotection, Mol, Belgium.
Int J Radiat Biol. 1990 Apr;57(4):677-91. doi: 10.1080/09553009014550851.
In mice, external X- or gamma-irradiation may induce thymic lymphomas or myeloid leukaemias, while bone-seeking alpha-emitters may induce osteosarcomas and, to a lesser extent, acute myeloid leukaemia. The present paper aims to review briefly some of the experimental data with respect to the molecular mechanisms underlying these radiation-induced carcinogenic processes. Thymic lymphomagenesis proceeds through an indirect mechanism. Recombinant proviruses often occur in the tumour cell DNA, favouring the idea that they might be involved. However, there are indications that they might mediate tumour growth rather than induction. It is plausible that activation of ras oncogenes by somatic point mutations might play a role in the carcinogenic process, although at a yet undetermined stage. Myeloid leukaemogenesis is characterized by a very early, putative initiating event, consisting of non-random rearrangements and/or deletions of chromosome 2. These may be related to deletions in the developmentally important homeobox gene clusters and to rearrangements of the sequences flanking the IL-1 beta gene. Either a gene of the homeobox family or IL-1 beta might be considered as potentially involved in the induction process. Osteosarcomagenesis in mice is often associated with the expression of proviruses, and the tumours often contain somatically acquired proviruses. These viruses may contribute to tumour development by affecting various growth-suppressor genes. Viruses isolated from bone tumours, although non-sarcomagenic, induce osteopetrosis, osteomas and lymphomas upon infection of newborn mice. Osteogenic tumours frequently display amplification of a region on mouse chromosome 15, which encompasses c-myc and Mlvi-1 sequences. Enhanced transcription of various oncogenes is found in individual tumours, but no specificity for osteosarcomas has been identified. In vitro systems of skeletoblast differentiation are being developed to study tumour induction in vitro.
在小鼠中，外部X射线或γ射线照射可能诱发胸腺淋巴瘤或髓性白血病，而亲骨性α发射体可能诱发骨肉瘤，在较小程度上还可诱发急性髓性白血病。本文旨在简要回顾一些关于这些辐射致癌过程潜在分子机制的实验数据。胸腺淋巴瘤的发生通过间接机制进行。重组前病毒经常出现在肿瘤细胞DNA中，这支持了它们可能参与其中的观点。然而，有迹象表明它们可能介导肿瘤生长而非诱导肿瘤发生。虽然尚不确定具体阶段，但体细胞点突变激活ras癌基因可能在致癌过程中起作用。髓性白血病的发生特点是一个非常早期的假定起始事件，包括染色体2的非随机重排和/或缺失。这些可能与发育重要的同源盒基因簇的缺失以及IL-1β基因侧翼序列的重排有关。同源盒家族的一个基因或IL-1β都可能被认为潜在参与诱导过程。小鼠骨肉瘤的发生通常与前病毒的表达相关，且肿瘤中常含有体细胞获得的前病毒。这些病毒可能通过影响各种生长抑制基因来促进肿瘤发展。从骨肿瘤中分离出的病毒，虽然不具有肉瘤致癌性，但在感染新生小鼠后可诱发骨质石化、骨瘤和淋巴瘤。成骨性肿瘤经常显示小鼠15号染色体上一个区域的扩增，该区域包含c-myc和Mlvi-1序列。在个别肿瘤中发现各种癌基因的转录增强，但尚未确定骨肉瘤的特异性。正在开发成骨细胞分化的体外系统以研究体外肿瘤诱导。
