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Abrogation of the G2 checkpoint results in differential radiosensitization of G1 checkpoint-deficient and G1 checkpoint-competent cells.
- Source :
-
Cancer research [Cancer Res] 1995 Apr 15; Vol. 55 (8), pp. 1639-42. - Publication Year :
- 1995
-
Abstract
- We have examined the effect of abrogation of the G2 checkpoint on the radiosensitivity of G1 checkpoint-proficient and G1 checkpoint-deficient cells. A549 human lung adenocarcinoma cells were transduced with the E6 oncogene of the human papillomavirus type 16 to eliminate their radiation-induced G1 arrest. These E6+ cells exhibited a dose-dependent increase in radiation resistance compared to control A549 cells transduced with the vector alone. Treatment (96 h) with 2 mM caffeine resulted in an abrogation of the cellular G2 checkpoint in both E6+ and control cells and a differential radiosensitizing effect on the two cell lines such that the E6+ clones and the vector controls became equally radiosensitive. These data show that human tumors which are radioresistant due to the loss of the p53-mediated G1 checkpoint can be made radiosensitive by abrogation of the G2 checkpoint. The implications of these results for cancer therapy are discussed.
- Subjects :
- Adenocarcinoma
Cell Division drug effects
Cell Division radiation effects
Cell Line
Cell Survival drug effects
Cell Survival radiation effects
Dose-Response Relationship, Radiation
Flow Cytometry
G1 Phase drug effects
G1 Phase physiology
G2 Phase drug effects
G2 Phase physiology
Genes, Viral
Humans
Kinetics
Lung Neoplasms
Nocodazole pharmacology
Oncogenes
Papillomaviridae genetics
Time Factors
Tumor Cells, Cultured
Caffeine pharmacology
G1 Phase radiation effects
G2 Phase radiation effects
Radiation-Sensitizing Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0008-5472
- Volume :
- 55
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 7712467