Mammalian cells in vitro will be studied in order to complete the definition of radiation killing, heat killing, and heat radiosensitization during the mammalian cell cycle, with emphasis on treating cells at the G1-S transition or in G2. Effects of lowering the pH and treating cells with membrane active agents and with agents that reduce concentrations of intracellular ATP will be studied. Endpoints will include cell killing, mutation induction, and chromosomal aberrations, as well as time of death or lysis as monitored by time lapse cinematography. Emphasis will be placed on studying the effects of low pH and nutrient deprivation on the indiction of thermotolerance and how the development and loss of thermotolerance is affected by cell cycle progression of viable cells. Also, the influence of low pH and nutrient deprivation of the effect of varying the sequence between heat and radiation will be studied. Finally, heat sensitive and heat resistant mutants, including hybrids of the two, will be obtained in order to relate heat killing with heat radiosensitization during the mammalian cell cycle.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA031813-05
Application #
3169940
Study Section
Radiation Study Section (RAD)
Project Start
1981-07-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Dewey, W C (2009) Arrhenius relationships from the molecule and cell to the clinic. Int J Hyperthermia 25:3-20
Vidair, C A; Doxsey, S J; Dewey, W C (1995) Thermotolerant cells possess an enhanced capacity to repair heat-induced alterations to centrosome structure and function. J Cell Physiol 163:194-203
Wong, R S; Dynlacht, J R; Cedervall, B et al. (1995) Analysis by pulsed-field gel electrophoresis of DNA double-strand breaks induced by heat and/or X-irradiation in bulk and replicating DNA of CHO cells. Int J Radiat Biol 68:141-52
Cedervall, B; Wong, R; Albright, N et al. (1995) Methods for the quantification of DNA double-strand breaks determined from the distribution of DNA fragment sizes measured by pulsed-field gel electrophoresis. Radiat Res 143:8-16
Dewey, W C; Ling, C C; Meyn, R E (1995) Radiation-induced apoptosis: relevance to radiotherapy. Int J Radiat Oncol Biol Phys 33:781-96
Dynlacht, J R; Wong, R S; Albright, N et al. (1994) Hyperthermia can reduce cytotoxicity from etoposide without a corresponding reduction in the number of topoisomerase II-DNA cleavable complexes. Cancer Res 54:4129-37
Dewey, W C (1994) Arrhenius relationships from the molecule and cell to the clinic. Int J Hyperthermia 10:457-83
Dewey, W C; Thompson, L L; Trinh, M L et al. (1994) A charge-coupled-device camera image analysis system for quantifying DNA distributions in agarose gels after pulsed-field gel electrophoresis. Radiat Res 140:37-47
Latz, D L; Trinh, M M; Thompson, L L et al. (1994) The effects of incorporation of bromodeoxyuridine into mammalian DNA on the migration patterns of DNA fragments subjected to pulsed-field gel electrophoresis after X irradiation or cutting with a restriction enzyme. Radiat Res 138:53-60
Vidair, C A; Dewey, W C (1993) Similar heat-induced cell cycle delays in the clonogenic and nonclonogenic fractions of a thermotolerant population. Radiat Res 133:265-7

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