RADIOPOTENTIATION OF HUMAN BRAIN-TUMOR CELLS BY THE SPERMINE ANALOG N-1,N-14-BIS(ETHYL)HOMOSPERMINE

Purpose: To determine whether the cytotoxicity produced by radiation c an be increased by the spermine analog N-1,N-14-bis(ethyl)homospermine (BE-4-4-4). Methods and Materials: Two human tumor cell lines, SF-126 and U-251 MG, were either treated with 0.1 or 0.4 mu M BE-4-4-4 for 3 or 4 days, or with 0.2 mu M BE-4-4-4 for 4 days. At the end of BE-4-4 -4 treatment, cells were irradiated and assayed immediately. Polyamine levels, cell survival, and cell number were determined. Results: In S F-126 cells, treatment with 0.2 mu M BE-4-4-4 for 4 days killed about 50% of the cells and also increased the cytotoxicity of radiation. The dose enhancement ratio was similar to 1.3:1.5, which is similar to th at reported for alpha-difluoromethylornithine. Polyamine levels were p artially depleted, and growth was inhibited to about 60% of control le vels. Pretreatment of cells with either 0.1 or 0.4 mu M BE-4-4-4 for 3 or 4 days produced less of an increase in radiation-induced cytotoxic ity, even though these exposures killed 30-40% or 60-90% of the cells, respectively. Similar treatment with 0.1-0.4 mu M BE-4-4-4 in U-251 M G cells had minimal effects on cytotoxicity and growth inhibition, whi le treatment with 1.0 mu M and 2.0 mu M BE-4-4-4 for 4 days produced m ore than a 50% depletion in polyamine levels and partial inhibition in growth, but failed to demonstrate radiopotentiation. Conclusion: The cytotoxic polyamine analog BE-4-4-4 can increase the cytotoxicity caus ed by radiation in at least one cell line. The amount of potentiation depends on the concentration of the analog, with the most occurring at the intermediate concentration. Because we did not observe potentiati on in both cell lines, and because of the dose dependence seen in SF-1 26 cells, the clinical efficacy produced by combined BE-4-4-4 and radi ation protocols may be limited.