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A p53 dose-response relationship for sensitivity to DNA damage in isogenic teratocarcinoma cells.
- Source :
-
Oncogene [Oncogene] 2001 May 24; Vol. 20 (23), pp. 2982-6. - Publication Year :
- 2001
-
Abstract
- Teratocarcinomas are tumors that arise from primordial germ cells and are readily curable with DNA-damaging chemotherapeutic drugs. Teratocarcinoma cells ex vivo in tissue culture are also relatively chemosensitive and undergo apoptotic death in response to DNA damage. We have previously hypothesized that the observed sensitivity of this tumor type to DNA damage is related to high basal expression of wild-type p53 protein. We have now addressed this issue by characterizing the DNA damage response of isogenic teratocarcinoma cells that differ only in their level of expression of wild-type p53 protein. We find a clear p53 dose-response relationship in these cells for rapid apoptosis following DNA damage that correlates with diminished colony formation in clonogenic survival assays. These results suggest that strategies to increase basal wild-type p53 protein expression prior to treatment with DNA-damaging drugs may improve curability in other tumor types.
- Subjects :
- 4-Nitroquinoline-1-oxide pharmacology
Animals
DNA Damage drug effects
Male
Mice
Teratocarcinoma drug therapy
Teratocarcinoma pathology
Testicular Neoplasms drug therapy
Testicular Neoplasms pathology
Tumor Cells, Cultured
Tumor Suppressor Protein p53 genetics
DNA Damage genetics
Teratocarcinoma genetics
Testicular Neoplasms genetics
Tumor Suppressor Protein p53 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0950-9232
- Volume :
- 20
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 11420711
- Full Text :
- https://doi.org/10.1038/sj.onc.1204394