The objective of this research is to understand the relationships between formation and repair of lesions in DNA at the molecular level and radiobiological phenomena at the cell or tissue level which are believed to be important to human cancer radiotherapy; including cellular recovery, the oxygen effect, the increased effectiveness of high LET radiation, and differences in radiosensitivity among tumor cells and normal cells. The experiments proposed will take advantage of new model systems and other relatively new technology to help address these questions. Specifically, we propose the following: (1) to investigate the role of DNA strand break rejoining mechanisms in cell survival and in recovery from sublethal and potentially lethal damage by use of repair-deficient mutants of Chinese hamster cells and inhibitors of DNA repair. (2) to investigate the long term time course of DNA strand break rejoining in normal and tumor tissues of mice irradiated in vivo. (3) to investigate possible explanations for the observed differences in efficiency of DNA strand break production among different normal and tumor tissues of mice irradiated in vivo. This study will include (a) measurements of the strand breaks produced under different conditions of oxygenation of the tissues (b) determination of the influence of radiation sensitizers on efficiency of break formation, and (c) measurements of normal and tumor tissue glutathione levels under different conditions of oxygenation. (4) to develop appropriate models based on the results of the aims above which will satisfactorily explain the role of unrepaired DNA strand breaks in cellular lethality both in vitro and in vivo. An important aspect of our approach is the application of the alkaline elution technique to the study of DNA strand break formation and repair in normal and tumor tissues of mice irradiated in-vivo with doses of ionizing radiation in the range used for therapeutic purposes. Ultimately, we hope that this approach will yield knowledge that can be exploited for the design of better regimens for radiotherapy of human cancer.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Radiation Study Section (RAD)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas MD Anderson Cancer Center
United States
Zip Code
Story, M D; Mendoza, E A; Meyn, R E et al. (1994) Pulsed-field gel electrophoretic analysis of DNA double-strand breaks in mammalian cells using photostimulable storage phosphor imaging. Int J Radiat Biol 65:523-8
Story, M D; Garrett, K C; Tofilon, P J et al. (1993) Influence of irradiation conditions on the measurement of DNA double-strand breaks by pulsed-field gel electrophoresis. Int J Radiat Biol 63:297-304
Meyn, R E; Murray, D; vanAnkeren, S C et al. (1991) Isolation and characterization of nitrogen mustard-sensitive mutants of Chinese hamster ovary cells. Mutat Res 254:161-5
Dolf, G; Meyn, R E; Curley, D et al. (1991) Extrachromosomal amplification of the epidermal growth factor receptor gene in a human colon carcinoma cell line. Genes Chromosomes Cancer 3:48-54
vanAnkeren, S C; Murray, D; Meyn, R E (1988) Induction and rejoining of gamma-ray-induced DNA single- and double-strand breaks in Chinese hamster AA8 cells and in two radiosensitive clones. Radiat Res 116:511-25
vanAnkeren, S C; Murray, D; Stafford, P M et al. (1988) Cell survival and recovery processes in Chinese hamster AA8 cells and in two radiosensitive clones. Radiat Res 115:223-37
Murray, D; Meyn, R E; Vanankeren, S C (1988) Variations in the spectrum of lesions produced in the DNA of cells from mouse tissues after exposure to gamma-rays in air-breathing or in artificially anoxic animals. Int J Radiat Biol Relat Stud Phys Chem Med 53:921-33
Murray, D; Meyn, R E (1987) Differential repair of gamma-ray-induced DNA strand breaks by various cellular subpopulations of mouse jejunal epithelium and bone marrow in vivo. Radiat Res 109:153-64
Murray, D; vanAnkeren, S C; Meyn, R E (1987) Applicability of the alkaline elution procedure as modified for the measurement of DNA damage and its repair in nonradioactively labeled cells. Anal Biochem 160:149-59
Cantoni, O; Murray, D; Meyn, R E (1987) Induction and repair of DNA single-strand breaks in EM9 mutant CHO cells treated with hydrogen peroxide. Chem Biol Interact 63:29-38

Showing the most recent 10 out of 14 publications