Polyamines and polyamine biosynthesis in cells exposed to hyperthermia
The issue of how polyamines act to sensitize cultured cells to the lethal effects of hyperthermia was investigated using Chinese hamster cells which were induced to express thermotolerance. Intracellular levels of these naturally occurring polycations were manipulated in certain situations by treating whole cells with methylglyoxal bis-(guanylhydrazone), an inhibitor of the S-adenosyl-L-methionine decarboxylases. Exogenous spermine as low as 100 ..mu..M in the culture media dramatically sensitized cells expressing thermotolerance to the lethal effects of subsequent 42/sup 0/C exposures. When thermotolerance was differentially induced in cultures exposed to 42.4/sup 0/C by varying the rate of heating from 37 to 42.4/sup 0/C, the most resistant cells and the highest levels of intracellular spermidine and spermine. This finding was explainable in part by the observation that the putrescine-dependent S-adenosyl-L-methionine decarboxylase activity was minimally affected in cells expressng the greatest degree of thermotolerance. When this enzyme activity was inhibited by drug, lowered intracellular polyamine levels did not correspond with subsequent survival responses to heat. Interestingly, cultures treated with methylglyoxal bis-(guanylhydrazone) 24 hr previous to heat exposure showed a reduced capacity to express rate of heating-induced thermotolerance. Together, these results demonstrate that the polyamines, especially spermidine and spermine, enhance hyperthermia-induced cell killing by some mechanism involving the plasma membrane. Further, our data suggest that methylglyoxal bis-(guanylhydrazone) can act to affect thermal responses by a mechanism(s) other than modification of intracellular polyamine levels.
- Research Organization:
- Univ. of Arizona Health Sciences Center, Tucson
- OSTI ID:
- 5848929
- Journal Information:
- Radiat. Res.; (United States), Journal Name: Radiat. Res.; (United States) Vol. 93:2; ISSN RAREA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
ANIMAL CELLS
ANIMALS
BODY TEMPERATURE
CELL CULTURES
CELL KILLING
CONNECTIVE TISSUE CELLS
DATA
ENZYME ACTIVITY
EXPERIMENTAL DATA
FIBROBLASTS
HAMSTERS
HYPERTHERMIA
INFORMATION
MAMMALS
NUMERICAL DATA
ORGANIC COMPOUNDS
PUTRESCINE
RESPONSE MODIFYING FACTORS
RODENTS
SENSITIVITY
SOMATIC CELLS
SPERMIDINE
SPERMINE
TEMPERATURE EFFECTS
TOLERANCE
VERTEBRATES