The toxic effect of spermidine on normal and transformed cells.

The cytotoxic effect of spermidine was investigated on various tissue culture cell lines in the presence of calf serum. Cells incubated with cytotoxic concentrations remained rounded up while cells in control cultures always spread out on the surface of the Petri dish. The spermidine concentration tolerated depends on cell number, concentration of serum, the strain of cells used and the phase of the growth cycle. The spermidine index (SI) of a cell culture is defined as the highest level of spermidine which did not show cytotoxic effect in the standard test system. The SI measures the ability of a cell culture (or line) to neutralize the cytotoxic effect of spermidine. The SI of normal fibroblastic cells such as BHK21IC13 or mouse embryo cells alters characteristically with different phases of the cell cycle. It is highest in lag or early exponential phase, then it diminishes during the exponential growth phase reaching its lowest point after the cell culture has become confluent. It is characteristic of polyoma virus-transformed cell lines and of other established permanent cell lines (which are probably of spontaneously transformed origin) that their SI decreases only slightly at high cell densities. There is a correlation between higher SI of transformed cells and their ability to grow in soft agar suspension.