APOPTOSIS INDUCED BY FAST-NEUTRONS VERSUS CO-60 GAMMA-RAYS IN HUMAN PERIPHERAL-BLOOD LYMPHOCYTES

Purpose: To investigate the effectiveness of high LET fast neutrons co mpared with low LET Co-60 gamma-rays to induce apoptosis in resting ly mphocytes. Materials and methods: Apoptosis induction was quantified b y light microscopic analysis of irradiated lymphocyte samples from hea lthy donors after 24 h culture. For the dose-response analyses doses r anging from 0.05 to 5 Gy were applied at 1.5 Gy/min (gamma-rays) or 0. 2 Gy/min (fast neutrons). To investigate the role of DNA repair in apo ptosis induction a dose of 2 Gy was also given at low dose-rate (0.006 Gy/min). Results: Dose-response curves obtained with both radiation q ualities were characterized by an initial steep increase in the number of apoptotic cells below 1 Gy, with a flattening of the curves at hig her doses towards 5 Gy. The calculated relative biological effectivene ss (RBE) values for fast neutrons were close to unity. When a 2 Gy dos e was administered at low rather than high dose-rate no decrease in ap optotic cell yield was observed. Conclusion: The dose-response data co nfirm the high radiosensitivity of lymphocytes and demonstrate that th eir response to undergo early interphase cell death by apoptosis is la rgely independent of LET. The observations that apoptosis induction is independent of LET and dose-rate may suggest that initial DNA damage, as opposed to DNA repair, dominate the induction of apoptosis in rest ing lymphocytes.