Synergistic antileukemic effect of theophylline and 1,3-bis(2-chloroethyl)-1-nitrosourea.
A series of experiments evaluated the antileukemic effect of an agent which elevates cellular cyclic adenosine 3':5'-monophosphate levels by phosphate levels by inhibiting phosphodiesterase. When administered alone, theophylline had only modest antileukemic effects, but it had synergistic effects when administered with 1,3-bis(2-chloroethyl)-1-nitrosourea. This synergism produced an improved therapeutic index in a dose-response study and in a comparison between antileukemic effects and effects on white blood cell nadirs. Uptake of 1,3-bis(2-chloroethyl)-1-nitrosourea and studies of timing of treatment support the hypothesis that elevation of cyclic adenosine 3':5'-monophosphate levels is the mechanism of the observed synergistic effect.
D000818:Animals; D002330:Carmustine / Q000378:metabolism / Q000627:therapeutic use*; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D013806:Theophylline / Q000627:therapeutic use*; D013997:Time Factors
D013806:Theophylline; D000242:Cyclic AMP; D002330:Carmustine