SPONTANEOUS IMMORTALIZATION OF CULTURED SKIN FIBROBLASTS OBTAINED FROM A HIGH-DOSE ATOMIC-BOMB SURVIVOR

Two immortal fibroblastic cell strains (substrains) were established b y culturing healthy skin cells obtained from a high-dose atomic bomb s urvivor (female, age 76 years, 5.14 Gy) for more than 4 years. Designa ted FM-U and FM-M, the two substrains share the same marker chromosome , t(5q-; 6p+), but are karyotypically different, possessing hypodiploi d chromosome numbers (39-43) in the former and hypertriploid (69-76) i n the latter. Thus far, the two strains have passed through 117 and 15 6 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 rear rangement among various chromosomes presumably due to telomeric and in terstitial telomeric fusions took place following the telomere shorten ing, 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 fr equency of cells possessing dicentric chromosomes.