G2M ARREST AND APOPTOSIS IN MURINE T-LYMPHOMA CELLS FOLLOWING EXPOSURE TO BI-212 ALPHA-PARTICLE IRRADIATION

Asynchronous exponentially growing EL4 murine T lymphoma cells were exposed either to high LET alpha-radiation from Bi-212-DTPA or to gamma-radiation from a Cs-137 source. Radiation-induced cell cycle perturbation was studied by flow cytometry. Alpha irradiation, like gamma, transiently arrested cells in the G2M phase in a dose-dependent manner. The maximum percentages of cells accumulated in G2M 18 h after alpha- and gamma-irradiation were comparable, though the dose-response relationships differed. The ''RBE'' value for G2M block for alpha- versus gamma-radiation was approx. 4. Electron microscopic studies of the cell samples where a large proportion of cells were arrested in G2M showed subcellular changes in nuclear membrane and the presence of morphologically apoptotic cells. Biochemical analysis of DNA from irradiated cells by agarose gel electrophoresis revealed more extensive DNA fragmentation for alpha- vs gamma-irradiation, even at relatively low total doses. We conclude that the high LET radiation is more efficient in inducing G2M block and apoptosis in EL4 lymphoma cells. The overall radiosensitivity of some high and low grade malignant lymphoma cells to radiation may correlate with these processes. The clinical implications of Bi-212-induced G2M delay may be particularly important for biologically targeted high LET radiopharmaceutical therapy.