Abstract

The use of radiotherapy in the treatment of cancer is based on the fact that ionizing radiation inhibits the proliferative capacity of tissues and results in cell death. The objective of this proposal is to study the effects of radiation in a related sequence of biochemical events which occur during the mammalian cell cycle and are involved in cell proliferation control. Previous studies have shown that the non-histone chromosomal proteins may be very important in the control of DNA replication, gene activation and cell division. The application proposes to study the effects of radiation on these proteins, as well as the enzymes and factors, specifically the protein kinases and cyclic nucleotides, which modify these proteins and possibly affect their regulatory functions. These studies should add fundamental insight to the understanding of radiation induced defects in cell cycle kinetics, and ultimately contribute to the optimization of the use of radiation for the treatment of human neoplastic disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA018273-11
Application #
3164904
Study Section
Radiation Study Section (RAD)
Project Start
1978-07-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
11
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Arizona
Department
Type
Schools of Medicine
DUNS #
City
Tucson
State
AZ
Country
United States
Zip Code
85722

  Publications

Gerner, E W; Tome, M E; Fry, S E et al. (1988) Inhibition of ionizing radiation recovery processes in polyamine-depleted Chinese hamster cells. Cancer Res 48:4881-5
Glass, J R; MacKrell, M; Duffy, J J et al. (1987) Ornithine decarboxylase production in vitro by using mouse cDNA. Biochem J 245:127-32
Donaldson, R W; Gerner, E W (1987) Phosphorylation of a high molecular weight DNA polymerase alpha. Proc Natl Acad Sci U S A 84:759-63
Glass, J R; Gerner, E W (1987) Spermidine mediates degradation of ornithine decarboxylase by a non-lysosomal, ubiquitin-independent mechanism. J Cell Physiol 130:133-41
Sertich, G J; Glass, J R; Fuller, D J et al. (1986) Altered polyamine metabolism in Chinese hamster cells growing in a defined medium. J Cell Physiol 127:114-20
Dorr, R T; Liddil, J D; Gerner, E W (1986) Modulation of etoposide cytotoxicity and DNA strand scission in L1210 and 8226 cells by polyamines. Cancer Res 46:3891-5
Gerner, E W; Mamont, P S; Bernhardt, A et al. (1986) Post-translational modification of the protein-synthesis initiation factor eIF-4D by spermidine in rat hepatoma cells. Biochem J 239:379-86
Gerner, E W; Mamont, P S (1986) Restoration of the polyamine contents in rat hepatoma tissue-culture cells after inhibition of polyamine biosynthesis. Relationship with cell proliferation. Eur J Biochem 156:31-5
Crossen, P E; Gerner, E W; Bell, C W et al. (1986) Analysis of the length of S-phase required to show sister chromatid differential staining. Cell Tissue Kinet 19:527-32
Glass, J R; Gerner, E W (1986) Polyamine-mediated turnover of ornithine decarboxylase in Chinese-hamster ovary cells. Biochem J 236:351-7

Showing the most recent 10 out of 11 publications