QUANTITATIVE DOSE-RESPONSE RELATIONS FOR THE CYTO-TOXIC ACTIVITY OF CHLOROETHYLNITROSOUREAS IN CELL-CULTURE

Google Scholar
  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (3) , 1008-1014
Abstract
A dose-response relation for the cytotoxic activity of chloroethylnitrosourea cancer chemotherapeutic agents in cell culture was developed. Data for the activity of 1,3-bis(2-chloroethyl)-1-nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea, and 1-(2-chloroethyl)-3-(piperidine-3,6-dion-3-yl)-1-nitrosourea against 9L rat brain tumor cells are presented. Cytotoxicity resulting from treatment schedules at different initial drug concentrations, exposure periods and preincubation periods are correlated using a proposed dose function. Equations are presented that incorporate drug concentration, duration of exposure of cells and the rate constant for conversion of the drug from an active intermediate into a single dose function. When compared in this way, all cell treatment schedules used were equally effective in killing cells in culture. The cytotoxic activity of the 4 different chloroethylnitrosourea analogs was also the same. These data demonstrate the application of quantitative dose-response relations to the activity of chloroethylnitrosoureas in cell culture and provide new insight into the mechanism of action and structure-activity relationships of these compounds.