Relationship of finite proliferative lifespan, senescence, and quiescence in human cells
โ Scribed by Gretchen H. Stein; Masayoshi Namba; Cheryl M. Corsaro
- Book ID
- 102885966
- Publisher
- John Wiley and Sons
- Year
- 1985
- Tongue
- English
- Weight
- 846 KB
- Volume
- 122
- Category
- Article
- ISSN
- 0021-9541
No coin nor oath required. For personal study only.
โฆ Synopsis
Cell hybrids were formed between human diploid fibroblasts (HDF) and carcinogen-transformed H D F to determine the relationship among: (1) finite proliferative lifespan, which we define as an age-related failure of a population to achieve one population doubling in 4 weeks; (2) arrest in a senescent state, which we define as cessation of D N A synthesis in a viable culture that is at t h e end of its lifespan by the above definition; and (3) arrest in a quiescent state, which we define as cessation of D N A synthesis in a young culture that is crowded or mitogen-deprived. H D F express all three of these phenotypes, which we have abbreviated FPL+, S + , and Q + , respectively. Carcinogentransformed H D F are transformed to immortality (FPL-) and inability to achieve quiescence (Q-). They have no S phenotype because, by definition, this phenotype only exists in FPL+ cells. Fusion of FPL+, Q+, S + HDF x FPL-, Q-carcinogen-transformed H D F produced hybrid clones that were FPL+, Q-, and S-, where the S -phenotype means that individual cells continued to synthesize DNA in cultures that had reached the end of their lifespan by our definition. These results are consistent with our hypothesis that senescent H D F and quiescent H D F may share a common mechanism for arrest in GI phase. We have suggested that this could occur if t h e aging mechanism that is responsible for the FPL+ phenotype is a progressive decrease in the ability of cells to recognize or respond to mitogenic growth factors. If so, then cells would become physiologically mitogen-deprived at
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