SV40LT Highly Mutates and Immortalizes Two Fibroblast Strains from Patients with Wilms' Tumor

Abstract

In order to analyze in detail the process of immortalization of human cells, SV40LT was introduced into two chromosome 11p- fibroblast strains from Wilms' 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 abnormally high while the crisis period of the CM2 strain was abnormally long. The CM1 immortalization was 7 times greater than the control and the CM2 strain 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 crisis 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 immortalization in vitro.