Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA045408-08
Application #
2091857
Study Section
Radiation Study Section (RAD)
Project Start
1987-09-01
Project End
1995-07-31
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
8
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Georgetown University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057

  Publications

Pang, Dalong; Rodgers, James E; Berman, Barry L et al. (2005) Spatial distribution of radiation-induced double-strand breaks in plasmid DNA as resolved by atomic force microscopy. Radiat Res 164:755-65
Kim, Kyoung M; Zhang, Yin; Kim, Bo-Yeon et al. (2004) The p65 subunit of nuclear factor-kappaB is a molecular target for radiation sensitization of human squamous carcinoma cells. Mol Cancer Ther 3:693-8
Kim, Bo-Yeon; Gaynor, Richard B; Song, Kyung et al. (2002) Constitutive activation of NF-kappaB in Ki-ras-transformed prostate epithelial cells. Oncogene 21:4490-7
Zhang, Y; Dimtchev, A; Dritschilo, A et al. (2001) Ionizing radiation-induced apoptosis in ataxia-telangiectasia fibroblasts. Roles of caspase-9 and cellular inhibitor of apoptosis protein-1. J Biol Chem 276:28842-8
Lee, S A; Dritschilo, A; Jung, M (2001) Role of ATM in oxidative stress-mediated c-Jun phosphorylation in response to ionizing radiation and CdCl2. J Biol Chem 276:11783-90
Jung, M; Dritschilo, A (2001) NF-kappa B signaling pathway as a target for human tumor radiosensitization. Semin Radiat Oncol 11:346-51
Pang, D; Chasovskikh, S; Cohen, J S et al. (2000) Atomic force microscopy examination of conformations of polynucleotides in response to platinum isomers: significance of GC content at broken ends. Int J Cancer 90:68-72
Prasad, S C; Soldatenkov, V; Notario, V et al. (1999) Detection of heterogeneity of apoptotic fragments of poly (ADP-ribose) polymerase in MDA-MB-468 breast cancer cells: two-dimensional gel analysis. Electrophoresis 20:618-25
Prasad, S; Soldatenkov, V A; Srinivasarao, G et al. (1999) Intermediate filament proteins during carcinogenesis and apoptosis (Review). Int J Oncol 14:563-70
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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