Jahan I, Bai L, Iijima M, Kondo T, Namba M
Department of Cell Biology, Okayama University Medical School, Japan.
Acta Med Okayama. 1995 Feb;49(1):25-8. doi: 10.18926/AMO/30417.
The establishment of a model system of neoplastic transformation of normal human cells has been attempted with a chemical carcinogen, 4-nitroquinoline 1-oxide (4NQO). In the course of these experiments, it was noticed that immortalization of human cells is a multi-step process involving several mutational genetic events. Thus, chromosomal changes which occurred during the process of immortalization of human fibroblasts were examined. To accomplish immortalization, fibroblasts obtained from an embryo were repeatedly treated with 10(-6) M 4NQO from primary culture to passage 51 (59 treatments in total). Before immortalization, some chromosomes (especially, chromosomes 2, 6, 8, 10, 11, 12, 15, 19, and 20), were lost at a relatively high frequency. After immortalization, the chromosomes distributed so broadly in the triploid to hypotetraploid region without a distinct modal number or without marker chromosomes that it was difficult to identify the specific chromosomes related to the immortalization of human cells. No specific structural chromosomal changes were detected. Although the significance of such chromosome changes in relation to immortalization is not clear, the loss of some specific chromosomes suggests that genes which are involved in cellular aging and which suppress immortalization may have been lost in the immortalization process.
人们尝试用化学致癌物4-硝基喹啉1-氧化物（4NQO）建立正常人细胞肿瘤转化的模型系统。在这些实验过程中，人们注意到人类细胞的永生化是一个涉及多个突变遗传事件的多步骤过程。因此，对人类成纤维细胞永生化过程中发生的染色体变化进行了研究。为实现永生化，从胚胎获取的成纤维细胞从原代培养到第51代（共59次处理）反复用10^(-6) M 4NQO处理。在永生化之前，一些染色体（特别是2号、6号、8号、10号、11号、12号、15号、19号和20号染色体）以相对较高的频率丢失。永生化后，染色体在三倍体到亚四倍体区域广泛分布，没有明显的众数或标记染色体，因此很难确定与人类细胞永生化相关的特定染色体。未检测到特定的染色体结构变化。尽管这种染色体变化与永生化的关系尚不清楚，但一些特定染色体的丢失表明，参与细胞衰老并抑制永生化的基因可能在永生化过程中丢失了。
