Measuring the spectrum of mutation induced by nitrogen ions and protons inthe human-hamster hybrid cell line A(L)C

Astronauts can be exposed to charged particles, including protons, alpha pa rticles and heavier ions, during space flights. Therefore, studying the bio logical 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 a nd densely ionizing 32 MeV/nucleon nitrogen ions using cells of two human-h amster cell lines, A(L) and A(L)C, We have previously characterized a spect rum of mutations, including megabase deletions, in human chromosome 11, the sole human chromosome in the human-hamster hybrid cell lines A(L)C and A(L ). CD59- mutants have lost expression of a human cell surface antigen encod ed 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 co ntrast, deletion of the 11p15.5 region is not lethal in the hybrid A(L)C, a llowing for the detection of chromosome loss or other chromosomal mutations involving 11p15.5, The 55 MeV protons and 32 MeV/nucleon nitrogen ions wer e each about 10 times more mutagenic per unit dose at the CD59 locus in A(L )C cells than in A(L) cells. In the case of nitrogen ions, the mutations ob served in A(L)C cells were predominantly due to chromosome loss events or 1 1p deletions, often containing a breakpoint in the pericentromeric region. The increase in the CD59- mutant fraction for A(L)C cells exposed to proton s was associated with either translocation of portions of 11q onto a hamste r chromosome, or discontinuous or "skipping" mutations. We demonstrate here that A(L)C cells are a powerful tool that will aid In the understanding of the mutagenic effects of different types of ionizing radiation. (C) 2000 b y Radiation Research. Society.