Changes in drug sensitivity of a human astrocytoma clone previously treated with 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea in vitro

Summary We have shown in earlier studies that repeated weekly exposures of a human astrocytoma clone (AST 3–4) to MeCCNU (10 g/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 g/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 g 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.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 Dedicated to the memory of Benjamin Drewinko, Physician, Scientist and friend.