Kraemer, S. M., Kronenberg, A., Ueno, A. and Waldren, C. A. Measuring the Spectrum of Mutation Induced by Nitrogen Ions and Protons in the Human–Hamster Hybrid Cell Line A_LC.

Astronauts can be exposed to charged particles, including protons, α particles and heavier ions, during space flights. Therefore, studying the biological effectiveness of these sparsely and densely ionizing radiations is important to understanding the potential health effects for astronauts. We evaluated the mutagenic effectiveness of sparsely ionizing 55 MeV protons and densely ionizing 32 MeV/nucleon nitrogen ions using cells of two human–hamster cell lines, A_L and A_LC. We have previously characterized a spectrum of mutations, including megabase deletions, in human chromosome 11, the sole human chromosome in the human–hamster hybrid cell lines A_LC and A_L. CD59^– mutants have lost expression of a human cell surface antigen encoded by the CD59 gene located at 11p13. Deletion of genes located on the tip of the short arm of 11 (11p15.5) is lethal to the A_L hybrid, so that CD59 mutants that lose the entire chromosome 11 die and escape detection. In contrast, deletion of the 11p15.5 region is not lethal in the hybrid A_LC, allowing for the detection of chromosome loss or other chromosomal mutations involving 11p15.5. The 55 MeV protons and 32 MeV/nucleon nitrogen ions were each about 10 times more mutagenic per unit dose at the CD59 locus in A_LC cells than in A_L cells. In the case of nitrogen ions, the mutations observed in A_LC cells were predominantly due to chromosome loss events or 11p deletions, often containing a breakpoint in the pericentromeric region. The increase in the CD59^– mutant fraction for A_LC cells exposed to protons was associated with either translocation of portions of 11q onto a hamster chromosome, or discontinuous or “skipping” mutations. We demonstrate here that A_LC cells are a powerful tool that will aid in the understanding of the mutagenic effects of different types of ionizing radiation.