This research project will apply molecular approaches to investigate the responses of human tumor cells to ionizing radiation. Radiobiologically well-characterized, low passage cell lines established from patients with squamous cell carcinomas of head and neck origin are categorized as displaying """"""""resistant"""""""" or """"""""sensitive"""""""" phenotypes to killing by ionizing radiation. The cells are then analyzed to determine differential gene expression, mechanisms of resistance related to oncogene expression, DNA damage and repair, and antisense mediated approaches to modulation of the resistant phenotypes. We will test the hypothesis that the responses of tumor cells to ionizing radiation (sensitivity or resistance) are the result of differential gene expression. Using the techniques of 2-D protein gel electrophoresis and microsequencing, cDNA subtraction hybridization, and vector mediated gene transfer, we will identify genes association with the radiation resistant or radiation sensitive phenotype. Our analysis of the roles of these genes in the radiation response of tumor cells will provide insight into the basic mechanisms of radiation killing and permit molecular strategies to improve the therapeutic ratio.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA045408-06
Application #
3188505
Study Section
Radiation Study Section (RAD)
Project Start
1987-09-01
Project End
1995-07-31
Budget Start
1992-08-01
Budget End
1993-07-31
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Georgetown University
Department
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
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Varghese, S; Schmidt-Ullrich, R K; Dritschilo, A et al. (1999) Enhanced radiation late effects and cellular radiation sensitivity in an ATM heterozygous breast cancer patient. Radiat Oncol Investig 7:231-7

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