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Radiation-induced Apoptosis in a Murine T-Cell Hybridoma

Department of Radiology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132

Induction of an apoptotic cell death was studied in a mouse T-cell hybridoma. Apoptosis was induced in these cells following exposure to dexamethasone, X-radiation, 43°C heat shock, A₂₅₄ light, and hydrogen peroxide. In 5-Gy-exposed cells, a radiation-induced G₂ phase cell cycle progression block was maximum by 8 h. The cells began to escape this progression block by 10 h. Nuclear DNA fragmentation and uptake of the vital dye trypan blue began at 12 and 14 h, respectively, and were complete by 28 h. X-radiation-induced cell death was diminished when cells were irradiated in the presence of dimethyl sulfoxide, indicating that cell death was induced by oxidative cell damage. Substitution of nuclear DNA with bromodeoxyuridine enhanced death in cells exposed to either X-radiation or A₃₁₀ light, indicating that apoptosis could be induced by DNA damage. The results are consistent with radiation-induced apoptosis being stimulated by oxidative DNA damage. DNA damage stimulates a long-lived signal which controls the expression of apoptosis. Apoptosis is expressed in the G₁ phase of the cell cycle subsequent to the cell irradiation.

Received 7/ 8/91. Accepted 12/ 3/91.

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