Nature 266, 653 - 655 (14 April 1977); doi:10.1038/266653a0

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

MARK A. RITTER^*†, JAMES E. CLEAVER^† & CORNELIUS A. TOBIAS^‡

^†Laboratory of Radiobiology, University of California, San Francisco, California 94143
^‡Donner Laboratory, University of California Berkeley, California 94720
^*Present address: Department of Physiology, Harvard University, School of Public Health, Boston, Massachusetts 02115.

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, -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 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 -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.

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