Changes in drug sensitivity of a human astrocytoma clone previously treated with 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea in vitro.
We have shown in earlier studies that repeated weekly exposures of a human astrocytoma clone (AST 3-4) to MeCCNU (10 micrograms/ml for 1 h per week) produced a linear decrease in survival over the first 3 weekly treatments. But, after that time these cells became progressively more resistant to the 10 micrograms/ml concentration of the agent. In the studies reported here we show that these previously treated cells were also less responsive to other doses ranging from 1 to 30 micrograms MeCCNU/ml. This change in sensitivity to MeCCNU was accompanied by collateral changes in response to other agents: resistance to BCNU and Galactitol, increased sensitivity to Adriamycin, and no change to ionizing radiation. These experiments suggest that once repeated treatments with a single agent cause a tumor cell population to become more resistant, sensitivity to other agents may also change unpredictably.
Barranco
S C
SC
Department of Radiation Therapy, University of Texas Medical Branch, Galveston 77550.
Townsend
C M
CM
Jenkins
V K
VK
Koester
S K
SK
Ho
B Y
BY
Reumont
K J
KJ
D001254:Astrocytoma / Q000473:pathology*; D002330:Carmustine / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells / Q000187:drug effects / Q000528:radiation effects; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D004376:Galactitol / Q000494:pharmacology; D006801:Humans; D012673:Semustine / Q000494:pharmacology
D004376:Galactitol; D012673:Semustine; D004317:Doxorubicin; D002330:Carmustine