The role of intracellular calcium in the cellular response to ionizing radiation
- Univ. of Chicago, IL (United States)
- Dana Farber Cancer Institute, Boston, MA (United States)
Calcium is required as a cofactor by primer recognition proteins involved in DNA synthesis and by protein kinase C (PKC), which is activated by ionizing radiation. Because these processes may be involved in radiation-mediated regulation of the progression of cells through the phases of the cell cycle, we studied the effects of the intracellular Ca{sup 2+} chelator, acetoxymethyl-1,2-bis(2-aminophenoxy)ethane-N,N,N{prime},N{prime}-tetraacetic acid (AM-BAPTA), on PKC activation, expression of c-jun and Gadd45 and distribution of cells in the phases of the cell cycle after irradiation. AM-BAPTA prevented ionizing-radiation-induced activation of PKC and expression of c-jun in cells of humor tumor cell lines. Conversely, calcium chelation had no effect on X-ray-induced expression of the Gadd45 gene. To determine whether changes in the intracellular Ca{sup 2+} concentration ([Ca{sup 2+}]{sub i}) occurred during irradiation, we measured [Ca{sup 2+}]{sub i} in single cells using fura-2-based microfluorimetry. There was no increase in [Ca{sup 2+}]{sub i} during or after irradiation of cells of the human tumor cell lines RIT-3, SQ-20B or HL-60 or normal human fibroblast strain IMR-90. The percentage of human tumor cells crossing the G{sub 1}/S-phase border was reduced by pretreatment with AM-BAPTA. These data indicate that calcium is required for ionizing radiation-induced cell cycle regulation and PKC activation, but that increases in [Ca{sup 2+}]{sub i} do not occur in cells of the cell lines irradiated in this study. 46 refs., 7 figs., 1 tab.
- OSTI ID:
- 79318
- Journal Information:
- Radiation Research, Journal Name: Radiation Research Journal Issue: 3 Vol. 138; ISSN RAREAE; ISSN 0033-7587
- Country of Publication:
- United States
- Language:
- English
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