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Suppression of tumorigenicity mediated by 5-azacytidine and associated with increased chromosome number
Abstract:
5-Azacytidine (5-azaC), a hypomethylating agent, was examined for the effect on a highly tumorigenic murine cell line, T984-15. While 20 of 20 untreated subclones of T984-15 produced tumors when injected into BALB/c nude mice, 14 of 15 T984-15 subclones that were treated for 24 hours with 5 micrograms 5-azaC/ml displayed suppressed tumorigenesis under identical conditions. Of the 14 clones that were suppressed, 12 were nontumorigenic and 2 showed a greatly increased latency. Chromosome analyses of 5-azaC-treated nontumorigenic clones revealed that, in contrast to untreated tumorigenic controls (median chromosome number 49-59), 9 of 10 5-azaC-treated nontumorigenic clones analyzed displayed an elevated chromosome complement (68-94 chromosomes/cell). The increase in chromosome number occurred progressively with time, following a single 24-hour 5-azaC treatment, indicating that 5-azaC was not selecting for a subpopulation of cells with an elevated chromosome complement. The evidence that the hypomethylating agent 5-azaC can suppress a cell's tumorigenic potential and that this suppression correlates with increased chromosome number suggests that 5-azaC modulates cellular phenotypes by mechanisms that involve alterations in a cell's chromosome complement.
Insights
The hypomethylating agent 5-azacytidine (5-azaC) suppressed tumor formation in a murine cell line. This suppression correlated with an increased chromosome number in treated cells, suggesting a link between chromosome complement and tumorigenic potential.
Area of Science:
- Cancer Biology
- Epigenetics
- Cell Biology
Background:
- Highly tumorigenic murine cell lines are crucial models for cancer research.
- Hypomethylating agents are known to influence cellular phenotypes.
Purpose of the Study:
- To investigate the effect of 5-azacytidine (5-azaC) on the tumorigenic potential of the T984-15 murine cell line.
- To explore the relationship between 5-azaC treatment, suppressed tumorigenesis, and chromosomal alterations.
Main Methods:
- Treatment of T984-15 murine cell line subclones with 5-azacytidine (5-azaC).
- Injection of treated and untreated subclones into BALB/c nude mice to assess tumorigenesis.
- Chromosome analysis of 5-azaC-treated and untreated subclones.
Main Results:
- 20 of 20 untreated subclones were tumorigenic.
- 14 of 15 5-azaC-treated subclones showed suppressed tumorigenesis.
- Nontumorigenic 5-azaC-treated clones exhibited an elevated chromosome number (68-94) compared to tumorigenic controls (49-59).
- Increased chromosome number was progressive and not due to selection of pre-existing cells.
Conclusions:
- 5-Azacytidine (5-azaC) can suppress the tumorigenic potential of the T984-15 murine cell line.
- Suppression of tumorigenesis by 5-azaC correlates with an increased chromosome number.
- 5-AzaC may modulate cellular phenotypes through alterations in chromosome complement.