KARYOTYPIC ANALYSIS IN THE PROCESS OF IMMORTALIZATION OF HUMAN-CELLS TREATED WITH 4-NITROQUINOLINE I-OXIDE

The establishment of a model system of neoplastic transformation of no rmal human cells has been attempted with a chemical carcinogen, 4-nitr oquinoline 1-oxide (4NQO). In the course of these experiments, it was noticed that immortalization of human cells is a multi-step process in volving several mutational genetic events. Thus, chromosomal changes w hich occurred during the process of immortalization of human fibroblas ts 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 immortalizatio n, some chromosomes (especially, chromosomes 2, 6, 8, 10, 11, 12, 15, 19, and 20), were lost at a relatively high frequency. After immortali zation, the chromosomes distributed so broadly in the triploid to hypo tetraploid region without a distinct modal number or without marker ch romosomes that it was difficult to identify the specific chromosomes r elated to the immortalization of human cells. No specific structural c hromosomal changes were detected. Although the significance of such ch romosome changes in relation to immortalization is not clear, the loss of some specific chromosomes suggests that genes which are involved i n cellular aging and which suppress immortalization may have been lost in the immortalization process.