Apoptosis induced by fast neutrons versus 60Co gamma -rays in human peripheral blood lymphocytes

Abstract

Purpose: To investigate the effectiveness of high LET fast neutrons compared with low LET 60Co gamma -rays to induce apoptosis in resting lymphocytes. Materials and methods: Apoptosis induction was quantified by light microscopic analysis of irradiated lymphocyte samples from healthy donors after 24 h culture. For the dose-response analyses doses ranging 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 apoptosis 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 qualities were characterized by an initial steep increase in the number of apoptotic cells below 1 Gy, with a flattening of the curves at higher doses towards 5 Gy. The calculated relative biological effectiveness (RBE) values for fast neutrons were close to unity. When a 2 Gy dose was administered at low rather than high dose-rate no decrease in apoptotic cell yield was observed. Conclusion: The dose-response data confirm the high radiosensitivity of lymphocytes and demonstrate that their response to undergo early interphase cell death by apoptosis is largely 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 resting lymphocytes.