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Increased frequencies of gene and chromosome mutations after X-irradiation in mouse embryonal carcinoma cells transfected with the bcl-2 gene
- Source :
- Japanese Journal of Cancer Research : Gann
- Publication Year :
- 2000
-
Abstract
- Preimplantation stage mouse embryos are known to be highly sensitive to the killing effect of DNA-damaging agents such as radiation. Interestingly, however, this stage of development is well protected from radiation induction of malformation and carcinogenesis in postnatal life. In recent years, it has become clear that the stem cells of preimplantation stage embryos undergo extensive apoptosis after DNA damage. It has been postulated that this apoptosis is likely to be responsible for the resistance to malformation, by excluding cells carrying deleterious DNA damage. We have tested the possible role of apoptosis in elimination of gene and chromosome mutations in undifferentiated mouse embryonal carcinoma cell line, F9, transfected with human bcl-2 cDNA. The colony radiosensitivity of F9 cells was not affected by overexpression of the bcl-2 gene, but the apoptotic cell death was suppressed, as examined by DNA ladder assay and Hoechst staining. This suppression was accompanied by an increase in the frequencies of hprt mutation and micronucleus formation after X-irradiation. These results support the idea that maintenance of genomic integrity during early development is likely to be executed by apoptotic elimination of cells at risk.
- Subjects :
- Cancer Research
Hypoxanthine Phosphoribosyltransferase
bcl‐2
Embryonal Carcinoma Stem Cells
DNA damage
Apoptosis
Biology
Gene mutation
medicine.disease_cause
Transfection
Radiation Tolerance
Chromosomes
Mice
medicine
Animals
Humans
Radiosensitivity
Cells, Cultured
Micronuclei, Chromosome-Defective
Mutation
Micronucleus Tests
Radiation
Embryonal carcinoma cell
Oncology
Proto-Oncogene Proteins c-bcl-2
Cancer research
Neoplastic Stem Cells
Stem cell
Carcinogenesis
Rapid Communication
Subjects
Details
- ISSN :
- 09105050
- Volume :
- 91
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Japanese journal of cancer research : Gann
- Accession number :
- edsair.doi.dedup.....a04278b73180fe5f9e38da114b48f7e1