The objective is to describe the molecular lesions induced in mammalian cells by hyperthermia and determine which of these lesions result in cell lethality. More specifically, we wish to differentiate between heat-induced lesions which, in themselves, cause cell lethality and those which radiosensitize the cells by interacting with x-ray-induced lesions. The general aim is: to continue with the studies of heat effects on DNA replicon initiation and chain elongation in relation to a possible mechanism for induction of chromosomal aberrations in cells heated during S phase; quantify the effects of heat on the number of radiation-induced single-strand breaks and the delay and extent of rejoining when heat is combined with x-rays either before, during, or after irradiation of cells during G1 or S phase; and compare various endpoints, with emphasis on transport and ion concentrations, when cells are heated during G1 or S phase. Changes in the endpoints will be quantified as a function of time after heating, including the interval of development of thermal tolerance. A particularly important parameter to study, as an index of intracellular damage from heat, will be cellular activity of polymerase-beta because loss of its activity correlates very well with both heat killing and heat radiosensitization during both thermally tolerant and nontolerant conditions. Effects on all of these endpoints will be compared as thermal sensitivity is changed by using heat sensitizers and heat protectors. Emphasis will be placed on identifying both direct effects of heat within the cell and on modification of these effects resulting from membrane damage.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA031808-06
Application #
3169925
Study Section
Radiation Study Section (RAD)
Project Start
1981-07-01
Project End
1987-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
6
Fiscal Year
1986
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
Chu, Kenneth; Leonhardt, Edith A; Trinh, Maxine et al. (2002) Computerized video time-lapse (CVTL) analysis of cell death kinetics in human bladder carcinoma cells (EJ30) X-irradiated in different phases of the cell cycle. Radiat Res 158:667-77
Forrester, H B; Albright, N; Ling, C C et al. (2000) Computerized video time-lapse analysis of apoptosis of REC:Myc cells X-irradiated in different phases of the cell cycle. Radiat Res 154:625-39
Leonhardt, E A; Trinh, M; Chu, K et al. (2000) Mutations induced in the HPRT gene by X-irradiation during G(1) or S: analysis of base pair alterations, small deletions, and splice errors. Mutat Res 471:19-Jul
Endlich, B; Radford, I R; Forrester, H B et al. (2000) Computerized video time-lapse microscopy studies of ionizing radiation-induced rapid-interphase and mitosis-related apoptosis in lymphoid cells. Radiat Res 153:36-48
Leonhardt, E A; Trinh, M; Chu, K et al. (1999) Evidence that most radiation-induced HPRT mutants are generated directly by the initial radiation exposure. Mutat Res 426:23-30
Forrester, H B; Vidair, C A; Albright, N et al. (1999) Using computerized video time lapse for quantifying cell death of X-irradiated rat embryo cells transfected with c-myc or c-Ha-ras. Cancer Res 59:931-9
Forrester, H B; Yeh, R F; Dewey, W C (1999) A dose response for radiation-induced intrachromosomal DNA rearrangements detected by inverse polymerase chain reaction. Radiat Res 152:232-8
Forrester, H B; Radford, I R; Dewey, W C (1999) Selection and sequencing of interchromosomal rearrangements from gamma-irradiated normal human fibroblasts. Int J Radiat Biol 75:543-51
Leonhardt, E A; Trinh, M; Forrester, H B et al. (1998) Persistent decrease in viability as a function of X irradiation of human bladder carcinoma cells in G1 or S phase. Radiat Res 149:343-9
Leonhardt, E A; Trinh, M; Forrester, H B et al. (1997) Comparisons of the frequencies and molecular spectra of HPRT mutants when human cancer cells were X-irradiated during G1 or S phase. Radiat Res 148:548-60

Showing the most recent 10 out of 48 publications