Haugen A, Ryberg D, Hansteen I L, Amstad P
Department of Toxicology, National Institute of Occupational Health, Olson, Norway.
Int J Cancer. 1990 Mar 15;45(3):572-7. doi: 10.1002/ijc.2910450333.
We have recently shown that normal human kidney epithelial (NHKE) cells were immortalized by treatment with Ni(II) alone. In the present study the immortalized human kidney cell line (IHKE) was transfected with a plasmid construct containing the v-Ha-ras oncogene (pZipras). After transfection, the cell lines formed tumors in athymic nude mice, whereas the ZipNeoSV(X)-transfected IHKE control cultures formed no tumors. Tumor cell lines (THKE) were established from the tumors in nude mice. These cells appear to be of human epithelial origin and express high levels of Ha-ras transcript. Karyotypic analysis was performed. The cell lines were tri-, tetra- or pentaploid. A consistent finding in the IHKE, IHKZE and THKE cells was increased numbers of chromosomes 17 and 7p+. Some marker chromosomes were identical in the IHKE and THKE cell lines, underlining their common origin and their possible importance in the carcinogenic process. This shows that the combined action of a chemical carcinogen [i.e., Ni(II)] and v-Ha-ras oncogene resulted in fully transformed human kidney epithelial cells, consistent with a step-wise progression of human epithelial cell transformation.
我们最近发现，仅用镍（II）处理就能使正常人肾上皮（NHKE）细胞永生化。在本研究中，将含有v-Ha-ras癌基因的质粒构建体（pZipras）转染到永生化人肾细胞系（IHKE）中。转染后，该细胞系在无胸腺裸鼠中形成肿瘤，而转染ZipNeoSV(X)的IHKE对照培养物未形成肿瘤。从裸鼠肿瘤中建立了肿瘤细胞系（THKE）。这些细胞似乎起源于人类上皮细胞，并高水平表达Ha-ras转录本。进行了核型分析。细胞系为三倍体、四倍体或五倍体。在IHKE、IHKZE和THKE细胞中一致发现17号染色体和7p+染色体数量增加。在IHKE和THKE细胞系中有一些标记染色体相同，这突出了它们的共同起源以及它们在致癌过程中可能的重要性。这表明化学致癌物[即镍（II）]和v-Ha-ras癌基因的联合作用导致了完全转化的人肾上皮细胞，这与人上皮细胞转化的逐步进展一致。
