I. Jahan et al., KARYOTYPIC ANALYSIS IN THE PROCESS OF IMMORTALIZATION OF HUMAN-CELLS TREATED WITH 4-NITROQUINOLINE I-OXIDE, Acta medica Okayama, 49(1), 1995, pp. 25-28
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.