Ionizing radiation (IR) results in apoptosis in a number of actively p
roliferating or immature cell types. The effect of IR on rat dorsal ro
ot ganglion (DRG) neurons was examined in dissociated cell cultures. A
fter exposure to LR, embryonic DRG neurons, established in cell cultur
e for six days, underwent cell death in a manner that was dose-depende
nt, requiring a minimum of 8 to 16 Gy Twenty-live per cent cell loss o
ccurred in embryonic day 15 (E-15) neurons, grown in cell culture for
6 days ('immature'), and then treated with 24 Gy IR. In contrast, only
2% cell loss occurred in E-15 neurons maintained in culture for 21 da
ys ('mature') and then treated with 24 Gy IR Staining with a fluoresce
nt DNA-binding dye demonstrated dumping of the nuclear chromatin typic
al of apoptosis. Initiation of the apoptosis occurred within 24 h afte
r exposure to IR. Apoptosis was prevented by inhibition of protein syn
thesis with cycloheximide-Apoptosis induced by IR occurred more freque
ntly in immature than in mature neurons. Immature DRG neurons have a l
ower concentration of intracellular calcium ([Ca2+](i)) than mature ne
urons. Elevation of [Ca2+](i) by exposure to a high extracellular pota
ssium ion concentration (35 mu M) depolarizes the cell membrane with a
resultant influx of calcium ions. The activation of programmed cell d
eath after nerve growth factor (NGF) withdrawal is inversely correlate
d with [Ca2+](i) in immature DRG neurons. When treated with high extra
cellular potassium, these immature neurons were resistant to IR exposu
re in a manner similar to that observed in mature neurons. These data
suggest that [Ca2+](i) modulates the apoptotic response of neurons aft
er exposure to LR in a similar manner to that proposed by the ''Ca2+ s
etpoint hypothesis'' for control of NGF withdrawal-induced apoptosis.