Honda T, Sadamori N, Oshimura M, Horikawa I, Omura H, Komatsu K, Watanabe M
Department of Radiobiology, Radiation Effects Research Foundation, Nagasaki, Japan.
Mutat Res. 1996 Jul 5;354(1):15-26. doi: 10.1016/0027-5107(96)00003-6.
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.
通过对一名高剂量原子弹幸存者（女性，76岁，受照剂量5.14 Gy）的健康皮肤细胞进行4年多的培养，建立了两株永生性成纤维细胞系（亚系）。这两个亚系分别命名为FM-U和FM-M，它们具有相同的标记染色体t(5q-;6p+)，但核型不同，前者为亚二倍体染色体数（39 - 43条），后者为超三倍体（69 - 76条）。到目前为止，这两株细胞系分别传代了117次和156次以上，或分别经历了230次和310次以上的累积群体倍增，前者每次传代需要4 - 6天，后者需要3 - 4天。在永生化过程中，随着端粒缩短，尤其是在衰老和衰老后阶段的细胞中，可能由于端粒和间插端粒融合导致各种染色体之间发生了连续重排。特别值得关注的是，在这些永生化细胞群体中证实了p53基因的杂合性缺失（LOH）。此外，p53基因LOH的等位基因模式也有所不同。在两株细胞系中都证明了进一步表明无限增殖的证据，如端粒延长和具有双着丝粒染色体的细胞频率显著降低。
