Temperature dependence of leukemic cell destruction by alkyl-lysophospholipids (NSC 324368)

Alkyl-analogs (ALP) of 2-lysophosphatidylcholine induce a progressive destruction of neoplastic cells by interfering with the continuous turnover of membrane phospholipids. Using leukemic blast cells from patients with acute forms of leukemia the effect of temperature was evaluated. It was found that temperature strongly influences the cytotoxic activity of ALP. High temperatures potentiate whereas a slight decrease in temperature reduces leukemic cell destruction by ALP. At temperatures below 30 degrees C even high doses of ALP will not destroy these tumor cells. Furthermore, cell destruction initiated at 37 degrees C can be abolished by lowering the incubation temperature to 25 degrees C. These biological data have been confirmed by biochemical studies, showing a temperature dependence of ALP adsorption not accompanied by a corresponding increase of alkyl-cleavage enzyme activity. The rate of membrane phospholipid turnover seems to be essential for temperature dependent ALP induced cell destruction.