High-LET radiations induce a large proportion of non-rejoining DNA breaks

Abstract

THE mechanisms by which mammalian cells are killed by ionising radiation have not been explained at the molecular level and radiations with a high linear energy transfer (LET) can provide an important tool for investing these mechanisms. High-LET radiations, such as neutrons, π-mesons and low-energy heavy ions are known to kill bacteria^1,2, yeast^3,4, and mammalian cells in vitro^5–9 more efficiently per unit dose than radiations with diffuse patterns of ionization, or low-LETs, such as γ or X rays. Other radiobiological phenomena associated with high-LET radiations are a reduced effect of chemical modifiers, for example, oxygen¹⁰, on cellular radiation sensitivity and reduction or loss of cellular ability to recover from radiation damage between split radiation doses^5,8. Because of these and other attributes, including the favourable depth–dose distribution of heavy ions and π-mesons, high-LET radiations are being actively considered for use in cancer radiation therapy^11,12, and a thorough understanding of their biological effects is necessary for them to be used to advantage clinically. We report here that, over an LET range of 1–1953 KeV µm⁻¹, there is an excellent correlation between the efficiency of exponential (single-hit) cell killing and the induction of non-rejoining DNA strand breaks, as measured on alkaline sucrose gradients. This correlation implies that non-rejoined breaks are a cause of cell death.