MODULATING CA2-INDUCED APOPTOSIS SUPPRESSES DNA FRAGMENTATION BUT DOES NOT ENHANCE CLONOGENIC SURVIVAL( IN RADIATION)

The role of intracellular Ca2+ in radiation-induced apoptosis was stud ied in a cell line derived from a mouse B-cell lymphoma (LY-TH). These cells had previously been shown to be sensitive to radiation and to d ie by apoptosis. The cell permeant Ca2+ chelator xymethyl-)1,2-bis(o-a minophenoxy)ethane-N,N,N',N'- tetraacetic acid (BAPTA/AM) reduced the DNA fragmentation characteristic of apoptosis but had no effect on clo nogenic survival. Intracellular Ca2+ concentrations measured using the fluorescent indicator fura-2 only slowly increased over control value s after cells were irradiated unlike the rapid increase observed in ot her systems. Our results indicate that modulating the endpoint of DNA fragmentation using some agents may not necessarily alter the cells' c ommitment to death as determined by clonogenic survival assays. This s uggests that such agents play a role downstream of early initiation st eps in apoptosis and modulate only particular features of apoptosis af ter the cell is committed to die.