TY - JOUR
T1 - Theophylline release of replicon initiation inhibition by nitrosoureas correlates with the synergistic killing in L1210 leukemia in vitro
AU - Ducore, Jonathan M
AU - Rosenstein, Barry S.
PY - 1985
Y1 - 1985
N2 - This report demonstrates the synergistic killing of murine L1210 leukemia in vitro by BCNU and theophylline as has previously been reported in vivo. Synergism is also seen with the related nitrosourea CNU plus theophylline. As measured on alkaline sucrose gradients and by pH-step alkaline elution, the nitrosourea-induced inhibition of DNA replicon initiation is completely reversed in the presence of theophylline. DNA interstrand crosslinking, the damage which usually correlates with nitrosourea cytotoxicity, is not increased by the combination of nitrosourea plus theophylline. At high nitrosourea doses, this interstrand crosslinking is reduced in the presence of theophylline. At least part of the mechanism of the two-drug synergism is the theophylline release of nitrosourea-induced DNA initiation inhibition. Some of the results have been presented at the Annual Meeting of the American Association for Cancer Research.
AB - This report demonstrates the synergistic killing of murine L1210 leukemia in vitro by BCNU and theophylline as has previously been reported in vivo. Synergism is also seen with the related nitrosourea CNU plus theophylline. As measured on alkaline sucrose gradients and by pH-step alkaline elution, the nitrosourea-induced inhibition of DNA replicon initiation is completely reversed in the presence of theophylline. DNA interstrand crosslinking, the damage which usually correlates with nitrosourea cytotoxicity, is not increased by the combination of nitrosourea plus theophylline. At high nitrosourea doses, this interstrand crosslinking is reduced in the presence of theophylline. At least part of the mechanism of the two-drug synergism is the theophylline release of nitrosourea-induced DNA initiation inhibition. Some of the results have been presented at the Annual Meeting of the American Association for Cancer Research.
UR - http://www.scopus.com/inward/record.url?scp=0021879396&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0021879396&partnerID=8YFLogxK
U2 - 10.1016/0167-8817(85)90048-3
DO - 10.1016/0167-8817(85)90048-3
M3 - Article
C2 - 4000148
AN - SCOPUS:0021879396
VL - 146
SP - 1
EP - 8
JO - Mutation Research DNA Repair Reports
JF - Mutation Research DNA Repair Reports
SN - 0167-8817
IS - 1
ER -