(Dr. Chris Wang, advisor)

"Cell Cycle Affects Accumulation of ß-5-o-Carboranyl-2’-Deoxyuridine (D-CDU) in Human Glioma Cell Line"

Abstract

To investigate the D- enantiomer of ß-5-o-Carboranyl-2’-Deoxyuridine (D-CDU) for its potential as an agent for boron neutron capture therapy (BNCT), experiments have been designed to determine whether cell cycle affects the accumulation of D-CDU in a human glioma cell line (U-251). U-251 cells were synchronized at various phases of the cell cycle by contact inhibition plus serum deprivation (G1) and thymidine (S). Fluorescence-Activated Cell Sorter (FACS) analysis was performed to verify cell synchronization protocols using a propidium iodide staining procedure followed by statistical examination by ModFit LT 2.0, which determined the percentage of cells in each phase of the cell cycle. The synchronized cells were then incubated with tritium labeled D-CDU, and assayed at multiple time points by reverse phase high performance liquid chromatography (HPLC) and liquid scintillation to determine drug accumulation for each representative phase. Results indicate there is a significant increase in the concentration of D-CDU and its metabolites accumulated in the S phase as compared to the G1 phase for all time points.