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Polyamine Content and Release during the Proliferation of Burkitt's Lymphoma Cells in Vitro¹

Biological Markers Laboratory, National Cancer Institute Frederick Cancer Research Center, Frederick, Maryland 21701

The cellular content and excretion of polyamines in relation to the cell cycle and proliferation kinetics of Burkitt's lymphoma cells in vitro were investigated. Quantitative relationships were established between the cellular content of polyamines and the growth kinetic parameters, including specific growth rate, labeling index, and cell viability. The intracellular content of putrescine, spermidine, and spermine was significantly correlated with the specific growth rate, suggesting that all the polyamines actively participate in the process of Burkitt's lymphoma cell proliferation. A negative correlation was found between the labeling index and the intracellular content of putrescine (r = –0.893); a positive correlation was observed between the labeling index and the ratios of spermidine to putrescine (0.888) and spermine to putrescine (0.855). In addition, the extracellular content of putrescine showed a positive correlation with the labeling index (0.613). The percentage of dead cells determined by trypan blue exclusion exhibited a high positive correlation with the intracellular content of putrescine (0.912).

Examination of the distribution pattern of polyamines with respect to the fraction of cells in each cell cycle stage during a 10-day growth period revealed that the accumulation of cells in G₁ was associated with a reduction of intracellular levels of spermidine and spermine.

In cultures synchronized by double thymidine blockade, maximal levels of intracellular spermidine and spermine contents occurred in S phase. Levels of intracellular putrescine were found to be lowest when the DNA content was lowest in early and mid-S phase, and to be highest when the DNA content was highest in late S and early G₂ + M.

¹ Research was sponsored by the National Cancer Institute under Contract NO1-CO-75380 with Litton Bionetics, Inc.

² To whom requests for reprints should be addressed.

Received 1/25/79. Accepted 3/22/79.