ras oncogenes and phenotypic staging in N-methylnitrosourea- and gamma-irradiation-induced thymic lymphomas in C57BL/6J mice.
ras oncogenes and phenotypic staging in N-methylnitrosourea- and gamma-irradiation-induced thymic lymphomas in C57BL/6J mice.
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发表时间：
1988-10
期刊：
影响因子：
11.2
通讯作者：
Elizabeth W. Newcomb;Jacob J. Steinberg;Angel Pellicer
中科院分区：
文献类型：
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作者：
Elizabeth W. Newcomb;Jacob J. Steinberg;Angel Pellicer
我们研究了放射和n -甲基亚硝基脲（NMU）处理的C57BL/6J小鼠胸腺淋巴瘤的发展阶段。血清学鉴定淋巴瘤细胞为携带MEL-14hi、H-2Khi和IL-2R+表面标记的皮质细胞群。根据这些参数，C57BL/6J小鼠的淋巴瘤细胞无论诱导剂或激活癌基因（ras或非ras）均相同。采用裸鼠致瘤性实验和病灶形成实验分析辐射和nmu诱导肿瘤的转化活性。在致瘤性实验中，8/10的nmu诱导肿瘤和12/15的辐射诱导肿瘤显示转化活性。对裸鼠转化体的Southern blot分析显示，8个nmu诱导的淋巴瘤dna中有8个存在K-ras转化序列，12个辐射诱导的淋巴瘤dna中有2个存在K-ras转化序列，12个辐射诱导的淋巴瘤dna中有5个存在N-ras转化序列。辐射诱导胸腺淋巴瘤的5种dna的非ras转化活性表明这些肿瘤中存在一种未知的致癌基因。在这个动物模型系统中，胸腺淋巴瘤发展的分期将允许在致癌物诱导疾病过程的早期研究癌基因激活。这些结果也强调了裸鼠实验对激活癌基因评分的高敏感性，并且可能也表明在nmu诱导的C57BL/6J小鼠淋巴瘤中K-ras激活的频率很高。
We have investigated stages of thymic lymphoma development in radiation and N-methylnitrosourea (NMU)-treated C57BL/6J mice. The lymphoma cell was identified serologically as a cortical population bearing MEL-14hi, H-2Khi, and IL-2R+ surface markers. According to these parameters in C57BL/6J mice the lymphoma cell was the same regardless of inducing agent or activated oncogene (ras or non-ras). Transforming activity in the radiation and NMU-induced tumors was analyzed using both the nude mouse tumorigenicity assay and the focus-forming assay. 8/10 NMU-induced tumors and 12/15 radiation-induced tumors showed transforming activity in the tumorigenicity assay. Southern blot analysis of the nude mouse transformants demonstrated K-ras transforming sequences in eight of eight NMU-induced lymphoma DNAs, two of 12 radiation-induced lymphoma DNAs and N-ras transforming sequences in five of 12 radiation-induced lymphoma DNAs. The non-ras transforming activity in five DNAs from radiation-induced thymic lymphomas indicates the presence of an unidentified oncogene(s) in these tumors. Staging of thymic lymphoma development in this animal model system will allow the study of oncogene activation early in the course of carcinogen-induced disease. These results also emphasize the high sensitivity of the nude mouse assay to score for activated oncogenes and might also indicate a high frequency of K-ras activation in NMU-induced lymphomas in C57BL/6J mice.