title: Modulating Ca2+ in radiation-induced apoptosis suppresses DNA fragmentation but does not enhance clonogenic survival.
abstract: The role of intracellular Ca2+ in radiation-induced apoptosis was studied 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 die by apoptosis. The cell permeant Ca2+ chelator (acetyoxymethyl-)1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tet raacetic acid (BAPTA/AM) reduced the DNA fragmentation characteristic of apoptosis but had no effect on clonogenic survival. Intracellular Ca2+ concentrations measured using the fluorescent indicator fura-2 only slowly increased over control values after cells were irradiated unlike the rapid increase observed in other systems. Our results indicate that modulating the endpoint of DNA fragmentation using some agents may not necessarily alter the cells' commitment to death as determined by clonogenic survival assays. This suggests that such agents play a role downstream of early initiation steps in apoptosis and modulate only particular features of apoptosis after the cell is committed to die.
authors.affiliation: Department of Physiology and Cell Biology, University of Texas Health Sciences Center at Houston, Medical School 77030, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Voehringer
authors.forename: M D
authors.initials: MD
authors.lastname: Story
authors.forename: R G
authors.initials: RG
authors.lastname: O'Neil
authors.forename: R E
authors.initials: RE
authors.lastname: Meyn
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D002118:Calcium / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002614:Chelating Agents / Q000494:pharmacology; D002999:Clone Cells / Q000528:radiation effects; D003593:Cytoplasm / Q000378:metabolism; D053938:DNA Fragmentation; D005720:Gamma Rays; D016393:Lymphoma, B-Cell / Q000473:pathology*; D051379:Mice; D014407:Tumor Cells, Cultured / Q000528:radiation effects
chemical_list: D002614:Chelating Agents; D002118:Calcium