EFFECTS OF ALPHA-DIFLUOROMETHYLORNITHINE ON THE GROWTH OF 9L RAT-BRAIN TUMOR MULTICELLULAR SPHEROIDS AND THEIR RESPONSE TO 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA
- 1 January 1984
- journal article
- research article
- Vol. 44 (2) , 577-581
Abstract
9L rat brain tumor cell spheroids were treated with .alpha.-difluoromethylornithine (DFMO) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) alone and in combination. In contrast to results obtained with 9L monolayer culture cells, very low concentrations of DFMO killed spheroid cell within 0.5 day after the start of treatment; cell kill was maximum within 2-3 days. DFMO cytotoxicity could be prevented by adding putrescine (1 mM) to the culture medium. DFMO significantly slowed and eventually stopped the growth of spheroids in a dose-dependent manner. Cells in all regions of DFMO-pretreated spheroids were sensitized to BCNU as measured by colony-forming efficiency; this sensitization was prevented when putrescine was added before BCNU. When used as single agents, a 3-day treatment with 10 mM DFMO or a 1-h treatment with BCNU (1.5 .mu.g/ml) produced similar growth delay, but used in combination, the 2 agents produced a much longer growth delay than that produced by either agent alone. Growth of spheroids treated continuously for up to 28 days with 10 mM DFMO ceased at .apprx. 7 times the volume at the time of treatment. When spheroid cells were treated for 1 h with BCNU (1.5 .mu.g/ml) and then were treated continuously with DFMO, growth plateaued at .apprx. 3.5 times the volume at the time of treatment; when spheroids were treated first with DFMO for 3 days, then with BCNU (1.5 .mu.g/ml) for 1 h, and then treated continuously with DFMO, growth plateaued at .apprx. 1.5 times the volume at the time of treatment. The number of clonogenic cells per spheroid that survived combination treatment also reflected the cytotoxic effects of the 2 drugs. The combined drug treatment was very effective in inhibiting growth of spheroids and in preventing an increase in the number of clonogenic cells per spheroid.This publication has 10 references indexed in Scilit:
- CELL-CYCLE AGE RESPONSE OF 9L CELLS TO 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA AND MODIFICATION BY ALPHA-DIFLUOROMETHYLORNITHINE1983
- FACTORS THAT INFLUENCE INITIATION AND GROWTH OF 9L RAT-BRAIN GLIOSARCOMA MULTICELLULAR SPHEROIDS1982
- Polyamines are necessary for the survival of human small-cell lung carcinoma in culture.Proceedings of the National Academy of Sciences, 1981
- SENSITIZATION OF 9L RAT-BRAIN GLIOSARCOMA CELLS TO 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA BY ALPHA-DIFLUOROMETHYLORNITHINE, AN ORNITHINE DECARBOXYLASE INHIBITOR1981
- POTENTIATION OF THE ANTI-TUMOR THERAPEUTIC EFFECTS OF 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA BY ALPHA-DIFLUOROMETHYLORNITHINE, AN ORNITHINE DECARBOXYLASE INHIBITOR1981
- Depletion of 9L rat brain tumor cell polyamine content by treatment with -?-difluoromethylornithine inhibits proliferation and the G1 to S transitionExperimental Cell Research, 1981
- Development of a 9L Rat Brain Tumor Cell Multicellular Spheroid System and Its Response to 1,3-Bis(2-chloroethyl)-1-nitrosourea and Radiation2JNCI Journal of the National Cancer Institute, 1980
- EFFECTS OF DL-ALPHA-METHYLORNITHINE ON PROLIFERATION AND POLYAMINE CONTENT OF 9L RAT-BRAIN TUMOR-CELLS1980
- SELECTIVE DISSOCIATION AND CHARACTERIZATION OF CELLS FROM DIFFERENT REGIONS OF MULTICELL TUMOR SPHEROIDS1980
- Inhibition of EMT6 tumor growth by interference with polyamine biosynthesis ; Effects of α-difluoromethyl- ornithine, an irreversible inhibitor or ornithine decarboxylaseLife Sciences, 1980