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The Radiosensitivity of Satellite Cells: Cell Cycle Regulation and Apoptosis

From a clinical perspective, skeletal muscles and their resident myogenic stem cells (i.e., satellite cells) are commonly exposed to significant doses of radiation. To ascertain whether irradiation inhibits satellite cell cycle progression, cells were given 5 Gy and assessed for DNA content using standard FACS methodologies. Soon after irradiation (6 hrs) satellite cells showed a marked increase (2.5‐fold) in cells at the G2/M border, the fraction of cells with a 2n complement of DNA remained high over the course of the experiment (48h). The increase in G2/M cells comes at the expense of replicating cells, as 5 Gy led to a steady decline in S‐phase cells over the first 18h following irradiation. The fraction of S‐phase cells did not recover over the subsequent 30h. As cells gradually escaped the initial block at G2/M they traversed into the block at G1/S by 12h where they accumulated at ~1.3‐fold higher levels. Poly(ADP‐ribose)polymerases (PARP) cleavage assays were used to determine if irradiated satellite cells undergo apoptosis. Apoptosis was generally increased and found to be dose‐responsive, with a relative peak occurring at 48h where apoptosis was elevated by ~1.7 fold over controls set to unity. Collectively, these data demonstrate that satellite cells are sensitive to clinically relevant doses of radiation. Further studies are needed to determine how this impacts the growth of skeletal muscle.