Role of intracellular pH and DNA polymerase activities in hyperthermic killing and modulation of cellular thermal sensitivity

Thesis/Dissertation · Thu Jan 01 04:00:00 EST 1987

OSTI ID:5513154

Chu, G L

To elucidate the mechanism of heat killing and heat radiosensitization and their enhancements by low pH, (1) whether heat induced changes in intracellular pH (pH{sub i}) or pH gradient across the plasma membrane was studied; (2) the relative importance of intracellular versus extracellular pH in cellular thermal sensitivity was determined; (3) the effect of hyperthermia on polymerases associated with DNA synthesis and repair was investigated. To address whether pH{sub c} or pH{sub i} determined the low pH sensitization of heat killing and heat radiosensitization, CHO cells were cultured in McCoy's 5a medium containing 0.005 N NaHCO{sub 3}. The low pH-adapted cells became partially resistant to low pH sensitization of hyperthermic killing and hyperthermic radiosensitization because of an increase in pH{sub i} compared to unadapted cells at the same pH{sub c}. Both survival from heat alone and the thermal enhancement ratio (TER) correlated with pH{sub i} and not pH{sub c}. To begin investigating mechanisms responsible for low intracellular pH enhancing heat damage, enzymes associated with DNA synthesis and repair were studied. Reports show that low pH sensitizes CHO cells to heat-induced loss of polymerase activities. Furthermore, cycloheximide (CHM) treatment before and during heating protected the cells from heat-induced cell killing, radiosensitization and loss of cellular DNA polymerase activities.

• Research Organization: California Univ., Berkeley, CA (USA)
• OSTI ID: 5513154
• Country of Publication: United States
• Language: English

Related Subjects

560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY TEMPERATURE
CELL CONSTITUENTS
CELL KILLING
CELL MEMBRANES
CHO CELLS
CYCLOHEXIMIDE
DNA POLYMERASES
DNA REPAIR
DRUGS
ENZYME ACTIVITY
ENZYMES
FUNGICIDES
HYPERTHERMIA
MEMBRANES
NUCLEOTIDYLTRANSFERASES
PESTICIDES
PH VALUE
PHOSPHORUS-GROUP TRANSFERASES
POLYMERASES
RADIOSENSITIVITY
RADIOSENSITIVITY EFFECTS
RECOVERY
REPAIR
SURVIVAL TIME
TRANSFERASES