High-Dose 111In Induces G1 Cell Cycle Arrest and Cell Death in Rat Bone Marrow Mesenchymal Stem Cells

Abstract

Purpose: This study was performed to evaluate the effect of 111In-labeling on the cell growth, cycle and viability of bone marrow mesenchymal stem cells (BMSCs). Methods: Rat BMSCs were labeled with various doses of 111In (0.4–11.1 Bq/cell). The growth curve of 111In-BMSCs was obtained up to 14th day of labeling. The cell cycle was evaluated by 5-bromo-2-deoxyuridine (BrdU) labeling or propidium iodide (PI) staining. Senescent cells were counted under a light microscope after staining with 5-bromo-4-chloro-3-indolyl-D-galactopyranoside. Flow cytometry was performed to measure apoptotic and necrotic fractions after staining with annexin V-FITC and PI. Results: The growth of BMSCs labeled with higher doses of 111In (4.4 or 11.1 Bq/cell) was significantly inhibited from the 3rd day of labeling. Flow cytometry revealed less BrdU-positive BMSCs at 11.1 Bq 111In/cell during all measurement days and G1 arrest at 4.4 and 11.1 Bq 111In/cell. Significant increases in apoptosis and necrosis were also observed at 4.4 (3.04%/1.35%) and 11.1 Bq 111In/cell (9.07%/3.18%) on the 14th day (control = 1.60%/0.39%). However, no cellular senescence was visualized up to the 14th day. Conclusion: A high dose of 111In-labeling induced cell cycle arrest and death in BMSCs; therefore, it should be used with a careful dosimetry in case of applying it to humans.