Polyamine content and release during the proliferation of Burkitt's lymphoma cells in vitro.

Abstract

changes in the urinary excretion of these markers correlated with disease response of patients to treatment. Polyamines are intimately involved in cell growth, and the most marked synthesis and accumulationof polyaminesoccur in rapidly growing tissues (27). The urinary excretion of poly amines in multiple myeloma patients receiving chemotherapy was correlated with the tnitiated thymidine labeling index of tumor cells in a subgroup of these patients. The occurrence of extracelbularpolyaminesin Ehnlichascites tumor-bearing mice during tumor growth was related to a continuous release from dead or dying tumor cells (8). In the MTW9 mammarytumor, intracellular spermidine levels, which increase during tumor growth, were lowered during tumor regression, and spermidine levels in the serum were considered to reflect tumor cell death (29). These results led to the concept that spermidine can serveas a markerof tumor cell kill, whereasputrescineappears to reflect the growth fraction of the tumor (4, 28). In a synchronous population of Chinese hamster cells ob tamed by selective detachment of mitotic cells, increases in spermidine and spermine occurred during 5, and they were correlated with passage through G, and entry into S (11, 30). The content of pobyaminesin AKR leukemia cells in mice increased progressively as the cells traversed the cell cycle from G, to M (14). We have studied the cellular content and excretion of poly amines in a Burkitt's lymphoma cell line grown in vitro to establish how the cellular pobyaminecontent changes in rela tion to the growth kinetics of Burkitt's lymphoma. The growth kinetics of Burkitt's lymphomacells in vitro has been charac terized and described in detail elsewhere (36). In the present study, the kinetic parameters of tumor growth, including the specific growth rate calculated from the growth curve, the labeling index, and the dead cell number,determinedby trypan blue exclusion, as well as the cell loss rate derived from cell cycle analysis, were correlated with the intra- and extracellular content of the polyamines. Analysis of the relationship between polyamines and cell cycle stages was carried out using the time sequence of the fraction of cells in each cycle stage during a 10-day growth period. The fraction of cells in each stage was obtained by analyzing DNA content distributions utilizing the discrete-time kinetic model(36). A cell population synchronized by meansof a double thymidine blockade was also studied to further eval uate the polyaminecontent in relation to the cell cycle.