Summary
We have shown in earlier studies that repeated weekly exposures of a human astrocytoma clone (AST 3–4) to MeCCNU (10 μg/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 μg/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 μg 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.
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Abbreviations
- DAG:
-
Galactitol
- Adria:
-
Adriamycin
- PCNU:
-
1-(2-Chloroethyl)-3-(2,6 dioxo-3-piperidyl-1-nitrosourea)
- MeCCNU:
-
1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea
- BCNU:
-
1,3-bis(2-chloroethyl)-1-nitrosourea
- FMF:
-
Flow microfluorometry
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Dedicated to the memory of Benjamin Drewinko, Physician, Scientist and friend.
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Barranco, S.C., Townsend, C.M., Jenkins, V.K. et al. Changes in drug sensitivity of a human astrocytoma clone previously treated with 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea in vitro . Invest New Drugs 6, 293–298 (1988). https://doi.org/10.1007/BF00173647
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DOI: https://doi.org/10.1007/BF00173647