Lymphocytes, especially thymocytes, are highly radiosensitive and undergo “interphase death” shortly after low-dose irradiation. In this study, reagents that inhibit Ca
2+-dependent signals were found to reduce radiationinduced interphase death in mouse thymocytes. Thymocytes irradiated
in vitro were incubated for appropriate time periods with a calcium (Ca) chelator, Ca channel blockers, protein kinase C (PKC) inhibitors, or calmodulin (CaM) inhibitors. Cell viability was then measured by trypan blue dye exclusion. Data obtained by chelation of Ca
2+ with EGTA indicated that interphase death was a Ca
2+-dependent process and that Ca
2+ was required in both the early and late stages of the process. Interphase death was strongly suppressed by the addition of Co
2+ and La
3+ ions which inhibit both receptor-operated and voltage-gated Ca channels, but not by the addition of specific voltage-gated Ca channel blockers. This suggests that Ca
2+ might enter through receptor-operated Ca channels into irradiated cells. Involvement of PKC in inducing interphase death was supported by the results of experiments with PKC inhibitors such as H-7 and staurosporin. Calmodulin appeared to be uninvolved in inducing cell death. These results suggest that the induction of radiation-induced interphase death requires Ca
2+, and that depletion of Ca
2+ or disturbance of the Ca
2+-dependent signal can reduce interphase death.
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