Our objective is to develop and apply suitable methods of cell cycle analysis with which the growth kinetics of cancer and normal cells from man and experimental animals can be understood in the context of cancer therapy with drugs and radiation. We are especially interested in flow cytometric methods of kinetic analysis because they offer the promise of powerful, sensitive, rapid and practical approaches to kinetic analysis under steady-state and in the midst of therapy. We are continuing kinetic technique development in vitro using Lewis Lung (LL) tumor cells, KHT tumor cells and a dual Chinese hamster ovary (diploid plus tetraploid cultures) cell system. Emphasis is currently on the response of these cells to multiple doses of cell cycle phase specific drugs such as cytosine arabinoside (ara-C), hydroxyurea (HU) and vincristine (VCR). As kinetic techniques are developed in vitro, they are applied to kinetic studies of the response of LL and KHT tumors in vivo. We are also developing high pressure liquid chromatographic techniques for the measurement of levels of drugs and drug metabolites during therapy for correlation with the cell cycle kinetic effects. Extensive computer programs are being developed for the analysis of our cell cycle and pharmacokinetic data.