Haugen A, Maehle L, Mollerup S, Rivedal E, Ryberg D
Department of Toxicology, National Institute of Occupational Health, Oslo, Norway.
Environ Health Perspect. 1994 Sep;102 Suppl 3(Suppl 3):117-8. doi: 10.1289/ehp.94102s3117.
Cellular progression to malignancy appears to require a number of distinct steps in which genetic damage in key regulatory genes accumulates. Immortalization, or escape from senescence, is considered to be one of the first phenotypic changes. Ni2+ treatment of normal human kidney epithelial (NHKE) cells in vitro resulted in immortalization of the cells IHKE cells). The combined action of Ni2+ and v-Ha-ras oncogene fully transformed the cells to tumorigenicity in athymic nude mice. Sequence analysis of DNA from IHKE cells revealed point mutation in the p53 gene at codon 238 with T-->C transition. These findings suggest that Ni-induced mutation in the p53 gene can be involved in the immortalization of the NHKE cells. The results also show that changes in the responses to EGF and TGF beta and in the expression of their receptors occur during malignant progression in vitro.
细胞向恶性肿瘤的进展似乎需要多个不同的步骤，其中关键调控基因中的遗传损伤会不断累积。永生化，即从衰老中逃脱，被认为是最早出现的表型变化之一。在体外对正常人肾上皮（NHKE）细胞进行镍离子（Ni2+）处理导致细胞（IHKE细胞）永生化。Ni2+与v-Ha-ras癌基因的联合作用使细胞在无胸腺裸鼠中完全转化为具有致瘤性。对IHKE细胞的DNA进行序列分析发现，p53基因第238密码子处发生了T→C转换的点突变。这些发现表明，镍诱导的p53基因突变可能参与了NHKE细胞的永生化过程。结果还表明，在体外恶性进展过程中，细胞对表皮生长因子（EGF）和转化生长因子β（TGFβ）的反应及其受体表达发生了变化。
