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 ex posed either to high LET alpha-radiation from Bi-212-DTPA or to gamma- radiation from a Cs-137 source. Radiation-induced cell cycle perturbat ion was studied by flow cytometry. Alpha irradiation, like gamma, tran siently arrested cells in the G2M phase in a dose-dependent manner. Th e maximum percentages of cells accumulated in G2M 18 h after alpha- an d gamma-irradiation were comparable, though the dose-response relation ships differed. The ''RBE'' value for G2M block for alpha- versus gamm a-radiation was approx. 4. Electron microscopic studies of the cell sa mples where a large proportion of cells were arrested in G2M showed su bcellular changes in nuclear membrane and the presence of morphologica lly apoptotic cells. Biochemical analysis of DNA from irradiated cells by agarose gel electrophoresis revealed more extensive DNA fragmentat ion for alpha- vs gamma-irradiation, even at relatively low total dose s. We conclude that the high LET radiation is more efficient in induci ng G2M block and apoptosis in EL4 lymphoma cells. The overall radiosen sitivity of some high and low grade malignant lymphoma cells to radiat ion may correlate with these processes. The clinical implications of B i-212-induced G2M delay may be particularly important for biologically targeted high LET radiopharmaceutical therapy.