Mechanism of spermidine cytotoxicity at 37 degrees C and 43 degrees C in Chinese hamster ovary cells.

Spermidine (SPD) cytotoxicity is mediated largely through SPD oxidation by serum amine oxidases at both 37 degrees C and 43 degrees C. Alkaline sucrose gradient data suggest random induction of DNA strand breaks. A dose response with time at 37 degrees C or 43 degrees C (constant SPD) or with SPD concentration (constant time at 43 degrees C) was observed in terms of both DNA strand breaks and cell survival. The generation of peroxide was demonstrated in the absence of cells by the addition of SPD to medium containing 10% fetal bovine serum. Toxicity of SPD was reduced in saline, with catalase-thiourea and aminoguanidine, and enhanced by prior depletion of glutathione. Thermotolerance induced 16 h previously did not protect against SPD toxicity, suggesting that the reactive species from spermidine oxidation and heat damage do not produce related subcellular lesions.