Interactions of BCNU, low pH, glucose and hyperthermia in cultured RIF cells.
The interactions of BCNU (1,3-bis[2-chloroethyl]-1-nitrosourea) with low pH, glucose and hyperthermia were studied in cultured RIF tumor cells. The effect of a mild heat treatment of 43 degrees C, 1 h at pH 7.4 on cell killing [surviving fraction (S) = 0.27 +/- 0.05, standard error of the mean (S.E.)] was significantly enhanced by pH 6.5 (S = 0.11 +/- 0.02, S.E.) and 50 mM D-glucose (S = 0.14 +/- 0.01, S.E.). When heat (43 degrees C, 1 h) was added to BCNU, cytotoxicity was increased approximately 14-fold over BCNU alone. Moreover, pH 6.5 increased killing with BCNU and heat by an additional factor of 28. The presence of glucose at 37 degrees C at either pH 6.5 or 7.4 reduced BCNU toxicity in a dose dependent fashion. However, the presence of glucose did not reduce cell killing by BCNU at 43 degrees C. As a result BCNU cytotoxicity was enhanced by approximately 2 orders of magnitude when tumor cell acidification (glucose and low pH) was combined with BCNU and heat.
Neilan
B A
BA
Department of Medicine, John L. McClellan Memorial Veterans Hospital, Little Rock, AR.
Jenkins
T L
TL
Henle
K J
KJ
Moss
A J
AJ
Nagle
W A
WA
D002330:Carmustine / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D014407:Tumor Cells, Cultured / Q000187:drug effects
D005947:Glucose; D002330:Carmustine