EXPOSURE TO ORNITHINE RESULTS IN EXCESSIVE ACCUMULATION OF PUTRESCINEAND APOPTOTIC CELL-DEATH IN ORNITHINE DECARBOXYLASE OVERPRODUCING MOUSE MYELOMA CELLS

Ornithine decarboxylase (ODC) is the first key enzyme in the biosynthe sis of polyamines, aliphatic polycations that are indispensable for th e process of mammalian cell proliferation. The mouse myeloma cell line , 653-1, massively overproduces ODC due to the amplification of an act ive ODC gene. The addition of ornithine to the growth medium of 653-1 cells results in a massive increase in the intracellular concentration of putrescine, followed by rapid cell death. Ornithine-treated 653-1 cells display fragmented nuclei, chromatin condensation, and an oligon ucleosome-sized DNA ''ladder''; consequently, their death can be descr ibed as apoptosis. Accumulation of putrescine in 653-1 cells is accomp anied by a rapid decrease of protein synthesis activity, suggesting th at protein synthesis inhibition may be the cause for the apoptotic dea th of 653-1 cells. However, since the apoptotic death provoked by expo sure of 653-1 cells to ornithine reached a maximal level earlier than that caused by cycloheximide, we conclude that protein synthesis inhib ition is unlikely to be the direct cause of the observed apoptotic cel l death.