Sensitization to heat by the polyamines and their analogs
The polyamines putrescine, spermidine, and spermine have been shown to sensitize Chinese hamster ovary (CHO) cells to the cytotoxic effects of elevated temperatures. This sensitization occurs in the order spermine greater than spermidine greater than putrescine. A series of homologs of the diamine putrescine demonstrated little variance in the degree of potentiation until a chain length equivalent to that of spermidine was employed (1,8-diaminooctane). Two compounds bearing structural similarities to spermidine gave rather different results when combined with heat. Methylglyoxal bis(guanylhydrazone) (MGBG), an antiproliferative drug, sensitized cells to heat, while S-2-(3-aminopropylamino)-ethyl phosphoric acid (WR-2721), a radioprotector, had no measureable effect on 43 degrees C-induced cytotoxicity. Together, these results point out the primary importance of two terminal amino groups separated by either carbon, or carbon and nitrogen, atoms in an aliphatic chain in the observed sensitization of heat-induced cytotoxicity by polyamines. These data suggest specific dimensional characteristics of the presumed negatively charged structure(s) with which the polyamines are interacting to elicit this effect.
- Research Organization:
- University of Arizona Health Sciences Center, Division of Radiation Oncology, Tucson
- OSTI ID:
- 5474980
- Journal Information:
- Radiat. Res.; (United States), Journal Name: Radiat. Res.; (United States) Vol. 95:1; 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
BIOLOGICAL EFFECTS
BODY TEMPERATURE
CADAVERINE
CARBONIC ACID DERIVATIVES
CHO CELLS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
HYPERTHERMIA
MEG
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PUTRESCINE
RADIOPROTECTIVE SUBSTANCES
SPERMIDINE
SPERMINE
STRUCTURE-ACTIVITY RELATIONSHIPS
TEMPERATURE EFFECTS
THIOLS