Radiopotentiation of human brain tumor cells by the spermine analog N1,N14-bis(ethyl)homospermine.
OBJECTIVE
To determine whether the cytotoxicity produced by radiation can be increased by the spermine analog N1,N14-bis(ethyl)homospermine (BE-4-4-4).


METHODS
Two human tumor cell lines, SF-126 and U-251 MG, were either treated with 0.1 or 0.4 microM BE-4-4-4 for 3 or 4 days, or with 0.2 microM 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 SF-126 cells, treatment with 0.2 microM 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 approximately 1.3:1.5, which is similar to that reported for alpha-difluoromethylornithine. Polyamine levels were partially depleted, and growth was inhibited to about 60% of control levels. Pretreatment of cells with either 0.1 or 0.4 microM BE-4-4-4 for 3 or 4 days produced less of an increase in radiation-induced cytotoxicity, even though these exposures killed 30-40% or 60-90% of the cells, respectively. Similar treatment with 0.1-0.4 microM BE-4-4-4 in U-251 MG cells had minimal effects on cytotoxicity and growth inhibition, while treatment with 1.0 microM and 2.0 microM BE-4-4-4 for 4 days produced more than a 50% depletion in polyamine levels and partial inhibition in growth, but failed to demonstrate radiopotentiation.


CONCLUSIONS
The cytotoxic polyamine analog BE-4-4-4 can increase the cytotoxicity caused 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 potentiation in both cell lines, and because of the dose dependence seen in SF-126 cells, the clinical efficacy produced by combined BE-4-4-4 and radiation protocols may be limited.
Chen
C Z
CZ
Department of Neurological Surgery, School of Medicine, University of California, San Francisco.
Hu
L J
LJ
Bergeron
R J
RJ
Marton
L J
LJ
Deen
D F
DF
D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D006801:Humans; D011073:Polyamines / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013096:Spermine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D011073:Polyamines; D011838:Radiation-Sensitizing Agents; C058306:N(1),N(14)-bis(ethyl)homospermine; D013096:Spermine