Estimation and prediction of cell cycle specific effects of anticancer drugs (Q1086186)

Understanding of cell cycle kinetic effects of anticancer drugs is in need of for improving the chemotherapeutic treatment of cancer. In this paper drug effects over more than one cell generation time are predicted on the basis of the results of a short term (8 hrs) stathmokinetic experiment with cultures of exponentially growing Friend erythroleukemia cells where the normal cell division cycle (of approximately 10-11 hrs) was blocked by a new synthesized anticancer drug. A complete ''drug action curve'' is estimated, i.e. the percentage of cells affected versus their position in successive subcompartments of the cell cycle is determined by flow cytometry. Only the transition time through the \(G_ 1\) phase is considered as random whereas the durations of all the other cell cycle phases are nonrandom. The distribution of cell residence time in \(G_ 1\) was estimated by the nonparametric procedure of ''isotonic regression'' based on exit curves which are obtained from stathmokinetic experiments. For lower drug concentrations the substitution of the drug action curve in a model of continuous exposure predicts rather successfully the major features of the continuous exposure kinetics. For higher drug concentrations the prediction failed for effects of the long term exposure to the drug.