Niwa O, Muto M, Suzuki F, Kominami R, Yokoro K
Department of Pathology, Hiroshima University, Japan.
J Radiat Res. 1991 Dec;32 Suppl 2:235-47. doi: 10.1269/jrr.32.supplement2_235.
The expression of oncogenes was studied in 12 types of 178 mouse tumors induced by radiations and chemicals. DNA was analyzed in tumors in which the overexpression of oncogenes was noted. Amplification of the myc oncogene was found in chemically induced sarcomas, but not in sarcomas induced by radiation. Activation of oncogenes by small mutations and the inactivation of tumor suppressor genes has to be taken in account in the radiation induction of mouse tumors. We therefore made further analyses of radiogenic thymomas. Loss of heterozygocity was revealed in directly induced thymomas by the deletions of allele specific minisatellite bands. Analysis of a hypervariable minisatellite locus also revealed that these thymoma cells suffered high recombinogenic activity during tumorigenesis. In addition, transfection of cellular DNA to normal Golden hamster cells identified the activated K-ras oncogene in the directly induced radiogenic thymomas. Indirectly induced radiogenic thymomas were tested similarly. Transformed cells from secondary transfection experiment were positive for the mouse-specific repetitious sequences, but devoid of mouse ras oncogenes. Indirectly induced radiogenic thymomas originate from unirradiated normal thymus cells transplanted in irradiated hosts. The spontaneous activation of oncogenes yet to be identified may therefore be involved in the development of this tumor.
在178个由辐射和化学物质诱导产生的小鼠肿瘤的12种类型中研究了癌基因的表达。对那些发现癌基因过表达的肿瘤进行了DNA分析。在化学诱导的肉瘤中发现了myc癌基因的扩增，但在辐射诱导的肉瘤中未发现。在小鼠肿瘤的辐射诱导过程中，必须考虑癌基因通过小突变的激活和肿瘤抑制基因的失活。因此，我们对辐射诱发的胸腺瘤进行了进一步分析。通过等位基因特异性小卫星带的缺失，在直接诱导的胸腺瘤中发现了杂合性缺失。对一个高变小卫星位点的分析还表明，这些胸腺瘤细胞在肿瘤发生过程中具有高重组活性。此外，将细胞DNA转染到正常的金黄地鼠细胞中，在直接诱导的辐射诱发胸腺瘤中鉴定出了激活的K-ras癌基因。对间接诱导的辐射诱发胸腺瘤进行了类似的测试。二次转染实验中的转化细胞对小鼠特异性重复序列呈阳性，但没有小鼠ras癌基因。间接诱导的辐射诱发胸腺瘤起源于移植到受辐照宿主中的未受辐照的正常胸腺细胞。因此，尚未确定的癌基因的自发激活可能与这种肿瘤的发生有关。
