抄録
Many lines of evidence indicate that immortalization of human cells is a rate-limiting step in their malignant transformation. We immortalized normal human fibroblasts with 60Co gamma rays (KMST-6 line) and 4-nitroquinoline 1-oxide (SUSM-1 and OUMS-24F lines). Immortalization of normal human cells with gamma rays and 4-nitroquinoline 1-oxide (4NQO) required repeated treatments, suggesting that several mutational events are involved in the immortalization process. The immortalization of human cells itself may be a multistep process. None of these immortalized cells showed either anchorageindependent growth or tumorigenicity and therefore were not malignant. It was possible to further transform the KMST-6 and OUMS-24F lines into malignant cells by treatment with the ras oncogene, but not by transfection with the mutant p53 gene. The immortalized cells showed epithelial-like morphology, prominent numerical and structural abnormalities, requirement of serum growth factors for their growth, enhanced or aberrant expression of c-myc, and elongation of telomere. It is clear from these observations that these immortalized human cell lines are useful for studying many of the factors that are known to contribute to cellular aging, immortalization, and malignant transformation of human cells.
