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A possible factor in genetic instability of cancer cells: stress-induced secreted proteins lead to decrease in
J J Boesen1, N Dieteren, E Bal
1MGC Department of Radiation Genetics and Chemical Mutagenesis, University of Leiden, The Netherlands.
Carcinogenesis
|December 1, 1992
Summary
Ultraviolet irradiation induces stress responses that increase mutation rates in mammalian cells. These UV-induced factors may play a role in cancer development and genetic instability.
Area of Science:
- Cellular biology
- Molecular genetics
- Cancer research
Background:
- Mammalian cells exhibit a UV response to ultraviolet irradiation, involving enhanced synthesis of extracellular proteins.
- Cancer-prone syndromes with genetic instability show similar protein synthesis without external stimuli, suggesting a link to carcinogenesis.
Purpose of the Study:
- To investigate the hypothesis that induced stress-responsive proteins contribute to carcinogenesis and genetic instability.
- To determine if UV-induced factors can enhance mutation rates in mammalian cells.
Main Methods:
- Mouse T lymphoma cells (GRSL13) were treated with conditioned medium from UV-induced cells.
- Experimental conditions, including cell density and medium composition, were varied to optimize the effect of UV-induced factors.
- Fluctuation analysis was used to assess mutation rates and their temporal dynamics.
Main Results:
- UV-induced factors enhanced the overall mutation rate by 1.8-fold (P < 0.01).
- Optimal enhancement (2.8-fold, P < 0.002) occurred under specific conditions: high-density, serum-starved cells treated with serum-free conditioned medium from high-density UV-irradiated cultures.
- Mutation rate enhancement reached 10-fold within the first five generations post-treatment.
- UV-induced factors also promoted cell growth, correlating linearly with mutation rate enhancement.
Conclusions:
- The induction of cellular stress responses, as triggered by UV irradiation, can lead to increased genetic instability.
- These findings support the hypothesis that stress-induced proteins are involved in the mechanisms underlying genetic instability and potentially carcinogenesis.