Analysis of radiation-induced apoptosis mechanism and its preventive factors in lymphocyte

To elucidate the mechanism of radiation-induced apoptosis, an investigation was made on the activation of caspase family by biochemical and immunological techniques. The family is thought to play an important role in apoptosis. MOLT cells (human T-cell leukemia CD-4 and CD-8) were used as the subjects and exposed to X-ray at 5 Gy. The time course changes in the activities of caspase 3, 7 and 9 were monitored using the respective specific substrates. Both activities of caspase 3 and 7 were increased from 6 hours after the exposure and only the latter was increased at 24 hours after that, suggesting that degradation or inactivation of caspase 3 might have occurred in an early time form the exposure. These activations of caspase 3 and 7 were examined with specific antibodies to both enzymes and inactivation of caspase 3 and 7 were confirmed in the control not-exposed, whereas it was confirmed that precursor molecules of caspase 3 and 7 began to increase from about 6 hours after the exposure. Twenty-four hours after the exposure, however, most of the precursor for caspase 3 disappeared and a half for caspase 7 remained. Caspase 3 has been reported to be not involved in radiation-induced apoptosis in the normal thymus cells and lymphocytes. The present study demonstrated for the first that both of caspase 3 and 7 were activated in radiation-induced apoptosis. Therefore, it was assumed that some caspase inhibitors might be useful to control radiation-induced apoptosis. (M.N.)