In order to analyze in detail the process of immortalization of human cells
, SV40LT was introduced into two chromosome 11p- fibroblast strains from Wi
lms' tumor patients. Both fibroblasts, hereafter referred to as CM1 and CM2
, displayed the mutant phenotype in the crisis stage of cellular aging. In
comparison to a control fibroblast, the density of the CM1 strain was abnor
mally high while the crisis period of the CM2 strain was abnormally long, T
he CM1 immortalization was 7 times greater than the control and the CM2 str
ain had the highest frequency of immortalization, 7 times greater than the
CM1. These findings indicate that genes associated with chromosome 11p- may
be involved in the immortalization of human cells. During their abnormal c
risis periods, the cells derived from the patients with Wilms' tumor showed
an extremely high frequency of chromosomal aberrations and mutations (6TG(
s) --> 6TG(r)). These results indicate that when the growth-arrested cells
from Wilms' patients are induced to grow with the introduction of SV40LT at
the crisis stage they are highly mutable, resulting in their immortalizati
on in vitro.