Spontaneous immortalization of cultured skin fibroblasts obtained from a high-dose atomic bomb survivor.

Two immortal fibroblastic cell strains (substrains) were established by culturing healthy skin cells obtained from a high-dose atomic bomb survivor (female, age 76 years, 5.14 Gy) for more than 4 years. Designated FM-U and FM-M, the two substrains share the same marker chromosome, t(5q-;6p+), but are karyotypically different, possessing hypodiploid chromosome numbers (39-43) in the former and hypertriploid (69-76) in the latter. Thus far, the two strains have passed through 117 and 156 subcultures or more than 230 and 310 cumulative population doublings, respectively, each passage requiring 4-6 days in the former and 3-4 days in the latter. In the process of immortalization, sequential rearrangement among various chromosomes presumably due to telomeric and interstitial telomeric fusions took place following the telomere shortening, particularly in the senescence and postsenescence phase cells. Of particular interest is the fact that loss of heterozygosity (LOH) of the p53 gene was demonstrated in these immortalized cell populations. In addition, the allelic patterns of the LOH of p53 differed. Further evidence indicative of infinite proliferation was demonstrated in both strains, such as the telomere elongation and the significantly low frequency of cells possessing dicentric chromosomes.