Coggin J H, Rohrer J W, Barsoum A L
University of South Alabama, College of Medicine, Department of Microbiology and Immunology, Mobile 36688, USA.
Int J Radiat Biol. 1997 Jan;71(1):81-94. doi: 10.1080/095530097144454.
Whole-body irradiation produces T-cell leukaemias/ lymphomas (TCL) in some strains of inbred mice in an X-ray dose-related manner. Radiation biologists have related the rapid "initiation' and early appearance of preleukaemic cells in these mice to unrepaired DNA damage inflicted by radiation. Following initiation, radiation-altered thymic differentiation fosters multi-step transformation changes in proto-oncogenes and suppressor gene expression in individual clones of non-invasive preleukaemia cells as they progress to malignancy. The malignant clones arising from small numbers of initiated preleukaemia thymocytes become fully transformed only after several more months to a year after irradiation in those strains of mice which develop T-cell lymphomas. When the RFM mouse was subjected to sublethal whole-body X-ray, only 50% of the mice developed TCL by 6 months, yet nearly all developed preleukaemia thymocytes. The T-cell-mediated immune response of the irradiated host has never been substantiated to contribute to malignant TCL development. Until recently, X-ray-induced TCL were not known to carry common tumour rejection antigens TATA. However, several studies have revealed that both preleukaemia cells and fully malignant TCL express an immunogenic, common oncofoetal glycoprotein, termed 44kD OFA. OFA-activated memory CD4 Tm and CD8 Ten. T-effector cells in irradiated mice expressing OFA. As most irradiated RFM mice exhibit preleukaemia thymocytes yet only half develop tumours, this finding implicates active host T-cell effector responses in X-ray-initiated tumorigenesis. Further, the recent discovery of OFA-specific CD8 Ts clones in irradiated mice, which inhibited cytotoxicity of CD8 clones to OFA or TSTA, may explain which mice develop T-cell lymphomas.
全身照射会以与X射线剂量相关的方式在某些近交系小鼠中诱发T细胞白血病/淋巴瘤（TCL）。辐射生物学家将这些小鼠中白血病前期细胞的快速“启动”和早期出现与辐射造成的未修复DNA损伤联系起来。启动后，辐射改变的胸腺分化促进了非侵袭性白血病前期细胞个体克隆中原癌基因和抑癌基因表达的多步转化变化，使其发展为恶性肿瘤。在那些发生T细胞淋巴瘤的小鼠品系中，由少量启动的白血病前期胸腺细胞产生的恶性克隆在照射后数月至一年才会完全转化。当RFM小鼠接受亚致死剂量的全身X射线照射时，6个月时只有50%的小鼠发生TCL，但几乎所有小鼠都出现了白血病前期胸腺细胞。照射宿主的T细胞介导的免疫反应从未被证实有助于恶性TCL的发展。直到最近，还不知道X射线诱导的TCL携带常见的肿瘤排斥抗原TATA。然而，几项研究表明，白血病前期细胞和完全恶性的TCL都表达一种免疫原性的、常见的癌胚糖蛋白，称为44kD OFA。OFA激活记忆性CD4 Tm和CD8 Ten。照射小鼠中表达OFA的T效应细胞。由于大多数受照射的RFM小鼠表现出白血病前期胸腺细胞，但只有一半发生肿瘤，这一发现表明宿主T细胞效应器的积极反应参与了X射线引发的肿瘤发生。此外，最近在受照射小鼠中发现了OFA特异性CD8 Ts克隆，它抑制了CD8克隆对OFA或TSTA的细胞毒性，这可能解释了哪些小鼠会发生T细胞淋巴瘤。
