Document Detail


Abrogation of the G2 checkpoint results in differential radiosensitization of G1 checkpoint-deficient and G1 checkpoint-competent cells.
MedLine Citation:
PMID:  7712467     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
K J Russell; L W Wiens; G W Demers; D A Galloway; S E Plon; M Groudine
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  55     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1995 Apr 
Date Detail:
Created Date:  1995-05-15     Completed Date:  1995-05-15     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1639-42     Citation Subset:  IM    
Affiliation:
Department of Radiation Oncology RC-08, University of Washington School of Medicine, Seattle 98195, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma
Caffeine / pharmacology*
Cell Division / drug effects,  radiation effects
Cell Line
Cell Survival / drug effects,  radiation effects
Dose-Response Relationship, Radiation
Flow Cytometry
G1 Phase / drug effects,  physiology,  radiation effects*
G2 Phase / drug effects,  physiology,  radiation effects*
Genes, Viral
Humans
Kinetics
Lung Neoplasms
Nocodazole / pharmacology
Oncogenes
Papillomaviridae / genetics
Radiation-Sensitizing Agents / pharmacology*
Time Factors
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
R01-CA58954/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Radiation-Sensitizing Agents; 31430-18-9/Nocodazole; 58-08-2/Caffeine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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