LIMITED IN VITRO LIFETIME OF HUMAN DIPLOID CELL STRAINS
LIMITED IN VITRO LIFETIME OF HUMAN DIPLOID CELL STRAINS
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DOI：
10.1016/0014-4827(65)90211-9
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发表时间：
1965-01-01
影响因子：
3.7
通讯作者：
HAYFLICK, L
中科院分区：
文献类型：
--
作者：
HAYFLICK, L
预期人二倍体细胞株停止体外分裂的时间（III期）不是继代培养次数的函数，而是潜在细胞倍增次数的函数。群体中的每个可克隆细胞被赋予相同的倍增潜力（50[±] 10）。将相同品系但具有不同“倍增潜力”的细胞混合。在这种混合群体中，III期发生在“最年轻”的细胞组分预期达到III期的时候。“较老”部分对“较新”部分中第三阶段预计发生的时间没有影响。确认了一个辅助结论，即III期不能通过存在潜伏病毒、支原体或培养基成分来解释。来自成人肺的人二倍体细胞株在体外的加倍潜力明显低于胎儿细胞株。III期现象可能与体内衰老有关。衰老的细胞理论必须与体外正常细胞有关，而不是异倍体细胞系。前者有一个有限的增殖期，后者是无限可培养的。体内实验还表明，移植的正常组织具有有限的寿命。在第三阶段中发生的染色体异常可能与包括人在内的老年动物细胞中发生的这种异常有关。用人二倍体细胞株获得的存活曲线与用其他生物系统获得的“多靶点”或“多靶点”曲线相当，其中在建立指数形式的曲线之前需要初始阈值剂量。无论人二倍体细胞株的有限寿命中可能涉及何种细胞组分，非分裂细胞的最终积累可能是对单个细胞靶标的累积损伤或对许多靶标的失活的结果。
The time at which human diploid cell strains can be expected to cease dividing in vitro (Phase III) is not a function of the number of subcultivations but rather of the number of potential cell doublings. Each clonable cell within the population is endowed with the same doubling potential (50[plus or minus] 10). Cells of the same strain, but with different "doubling potentials", were mixed. Phase III in such mixed populations occurs at that time when the "youngest" cell component is expected to reach Phase III. The "older" component has no effect on the time at which Phase III is expected to take place in the "younger" component. An ancillary conclusion that Phase III cannot be explained by the presence of a latent virus, mycoplasma or media composition is confirmed. Human diploid cell strains derived from adult lung have a significantly lower doubling potential in vitro than do fetal strains. The Phase III phenomenon may be related to senescence in vivo. The cellular theory of aging must be related to normal cells in vitro and not to heteroploid cell lines. The former have a finite period of multiplication; the latter are indefinitely cultivable. In vivo experiments also indicate that transplanted normal tissue has a finite lifetime. Chromosome anomalies occurring in Phase III may be related to such anomalies occurring in the cells of older animals, including man. The survival curves obtained with human diploid cell strains are comparable to "multiphle -hit" or "multiple -target" curves obtained with other biological systems where an initial threshold dose is required before an exponential form of the curve is established. Whatever cell component (s) may be involved in the finite lifetime of human diploid cell strains, the ultimate accumulation of non -dividing cells could be the result of accumulated damage to a single cellular target or to inactivation of many targets.