TY - JOUR
T1 - Cell cycle age response of 91 cells to 1, 3-bis(2-chloroethyl)-1-nitrosourea and modification by α-difluoromethylornithine
AU - Bjerkvig, Rolf
AU - Oredsson, Stina M.
AU - Marton, Laurence J.
AU - Linden, Margareta
AU - Deen, Dennis F.
PY - 1983/4/1
Y1 - 1983/4/1
N2 - We have determined the cell cycle age response of 9L rat brain tumor cells to 1, 3-bis(2-chloroethyl)-1-nitrosourea using centrifugal elutriation to obtain populations of cells enriched in G1, S, and G2-M phases. While cells in all phases of the cell cycle were killed by 20 or 40 μm 1, 3-bis(2-chloroethyl)-1-nitrosourea, cells in G1and G2-M phases were more sensitive than cells in S phase. The differential sensitivity was more pronounced at the higher dose, which will markedly alter the distribution of cells through the cell cycle. In a clinical setting, this factor could affect the efficacy of either fractionated or multimodality protocols. Treatment with α-difluoromethylomithine, a polyamine biosynthesis inhibitor, potentiated the cytotoxic effects of 20 μm 1, 3-bis(2-chloroethyl)-1-nitrosourea against G1- and G2-M- but not against S-phase cells; however, at a higher dose of 1, 3-bis(2-chloroethyl)-1-nitrosourea (40 μM), the cytotoxicity was potentiated for cells in all phases of the cell cycle. In α-difluoromethylomithine-treated cells, the phenomenon could be reversed by adding 1 mM putrescine 24 hr before treatment with 1, 3-bis(2-chloroethyl)-1-nitrosourea. Therefore, the potentiation of 1, 3-bis(2-chloroethyl)-1-nitrosourea cytotoxicity appears to be related to polyamine depletion.
AB - We have determined the cell cycle age response of 9L rat brain tumor cells to 1, 3-bis(2-chloroethyl)-1-nitrosourea using centrifugal elutriation to obtain populations of cells enriched in G1, S, and G2-M phases. While cells in all phases of the cell cycle were killed by 20 or 40 μm 1, 3-bis(2-chloroethyl)-1-nitrosourea, cells in G1and G2-M phases were more sensitive than cells in S phase. The differential sensitivity was more pronounced at the higher dose, which will markedly alter the distribution of cells through the cell cycle. In a clinical setting, this factor could affect the efficacy of either fractionated or multimodality protocols. Treatment with α-difluoromethylomithine, a polyamine biosynthesis inhibitor, potentiated the cytotoxic effects of 20 μm 1, 3-bis(2-chloroethyl)-1-nitrosourea against G1- and G2-M- but not against S-phase cells; however, at a higher dose of 1, 3-bis(2-chloroethyl)-1-nitrosourea (40 μM), the cytotoxicity was potentiated for cells in all phases of the cell cycle. In α-difluoromethylomithine-treated cells, the phenomenon could be reversed by adding 1 mM putrescine 24 hr before treatment with 1, 3-bis(2-chloroethyl)-1-nitrosourea. Therefore, the potentiation of 1, 3-bis(2-chloroethyl)-1-nitrosourea cytotoxicity appears to be related to polyamine depletion.
UR - http://www.scopus.com/inward/record.url?scp=0020585310&partnerID=8YFLogxK
M3 - Article
C2 - 6403224
AN - SCOPUS:0020585310
SN - 0008-5472
VL - 43
SP - 1497
EP - 1500
JO - Cancer Research
JF - Cancer Research
IS - 4
ER -