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Immortalization of Syrian hamster embryo cells: probabilistic event or deterministic process
B L Bols1, K C Gillis, J M Naaktgeboren
1MGC-Department of Radiation Genetics and Chemical Mutagenesis, University of Leiden, The Netherlands.
Cancer Research
|October 15, 1993
Summary
12-O-tetradecanoyl-phorbol-13-acetate (TPA) does not increase immortalization rates in SHE cells but extends their lifespan by interfering with cellular senescence. Epigenetic alterations in differentiation may drive immortalization and genetic instability.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- The activation/alteration hypothesis explains cell immortalization via carcinogen-induced
Purpose of the Study:
- Investigate the analogy between TPA-induced genetic instability and immortalization in SHE cells.
- Examine TPA's effect on SHE cell immortalization and lifespan.
- Explore the role of differentiation programs in cell immortalization and genetic instability.
Main Methods:
- Treatment of SHE cells with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and benzo(a)pyrene.
- Assessment of immortalization rates and cell culture lifespan.
- Analysis of correlations between lifespan, growth rate, and cell density.
Main Results:
- TPA did not affect the rate of immortalization but extended SHE cell lifespan.
- Lifespan correlated with growth rate and density at confluence, suggesting regulation of cellular senescence.
- Benzo(a)pyrene caused premature senescence in most cells but extended lifespan in a fraction, leading to immortalization.
- Repeated shifts between logarithmic growth and G0 enhanced lifespan and immortalization.
Conclusions:
- The "activated state" in immortalization involves a disturbance of differentiation programs, specifically cellular senescence in SHE cells.
- Epigenetic alterations driving deterministic dedifferentiation in subpopulations are a plausible explanation for immortalization, potentially more so than probabilistic mutations.
- Disturbances in cellular differentiation may contribute to genetic instability.