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Lethal, Potentially Lethal, and Nonlethal Damage Induction by Heavy Ions in Cultured Human Cells

Paul Todd, James C. S. Wood, James T. Walker and Steven J. Weiss
Radiation Research
Vol. 104, No. 2, Part 2: Supplement 8. Heavy Charged Particles in Research and Medicine (Nov., 1985), pp. S5-S12
DOI: 10.2307/3576625
Stable URL: http://www.jstor.org/stable/3576625
Page Count: 8
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Lethal, Potentially Lethal, and Nonlethal Damage Induction by Heavy Ions in Cultured Human Cells
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Abstract

In the fields of high-LET radiotherapy and space radiation safety it is important to know the relative probabilities with which a cell whose nucleus is struck by a heavy ion will be damaged or killed. Experiments were performed in which synchronous cultured human T-1 cells (presumptive HeLa) were irradiated with natural alpha particles of energy approximately 3.5 MeV at various times after mitotic selection up to the middle of S phase. Nuclear-area histograms were determined as a function of time after mitosis under conditions identical to those used for irradiation. The efficiency with which one particle passing through the nucleus killed a cell was found to be 0.14-0.20. This value was extrapolated to experimental cell survival data obtained when asynchronous cultured human cells were irradiated with He, Li, B, C, N, O, Ne, Ar ions of energy 6.58 or 5.5 MeV/amu, and the cell killing efficiency was found to be in the broad range of 0.5-1.0 under single-hit conditions. Similarly irradiated cells were examined for colony-size distribution by an image analysis technique, and it was found that the loss of large colonies was dose and LET-dependent in a systematic way. Dose-response data suggest two predominant subpopulations, resistant and sensitive cells, and it appears that the sensitive population is affected by single-hit kinetics. The single-hit coefficient for the induction of inherited slow growth varied with LET in a similar way to that for survival. The action cross section for this form of heritable damage appears to be comparable to the geometric cross section of the cell nucleus. In mitotic delay studies, irradiation with alpha-particle fluence corresponding to slightly more than one particle per nucleus resulted in a temporary mitotic index of zero. These studies and others lead to the conclusion that cells that survive heavy-ion traversals through their nuclei can be, and usually are, damaged in an LET-dependent manner. These findings are consistent with the discovery that heavy ions induce cataracts and tumors in vivo (both likely to be due to surviving cells) with very high efficiency.

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