Open AccessIncreased Frequencies of Gene and Chromosome Mutations after X‐Irradiation in Mouse Embryonal Carcinoma Cells Transfected with the bcl‐2 Gene
Author(s) -
Taga Masataka,
Shiraishi Kazunori,
Shimura Tsutomu,
Uematsu Norio,
Oshimura Mitsuo,
Niwa Ohtsura
Publication year - 2000
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.2000.tb00876.x
Subject(s) - biology , carcinogenesis , transfection , microbiology and biotechnology , dna damage , apoptosis , radiosensitivity , programmed cell death , gene , cancer research , genetics , dna , medicine , radiation therapy
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.