Distribution of breakpoints and fragment sizes in human chromosome 5 after heavy-ion bombardment

Purpose: To measure the location of heavy ion-induced residual breakpoints in human chromosome 5 and the size distribution of chromosome fragments involved in inter- or intrachromosomal exchanges. Materials and methods: Human peripheral blood lymphocytes were exposed to 4 Gy accelerated 56Fe (iron) ions (500 MeV per nucleon (MeV n^-1), linear energy transfer=200 keV (mu)m^-1). Cells were then stimulated to grow in vitro for 48 h, and chromosomes were prematurely condensed by calyculin A. Chromosome 5 was painted using high-resolution multicolour banding. The location of the observed residual breakpoints and the size of all chromosome 5 fragments involved in structural aberrations were measured using dedicated image analysis software. Results: Mapping of 283 breakpoints revealed a slight deviation from randomness, with an excess of breakpoints clustered in two small bands and an under representation of breaks at the telomeric end in the q-arm. Breakpoints per unit length were similar in p- and q-arms. The distribution of chromosome fragments has a maximum for very small fragments (<10% of the chromosome size), indicating a severe fragmentation of chromosome 5 after heavy-ion bombardment. Only fragments <40% of the chromosome size were involved in intrachromosomal exchanges (interstitial deletions or inversions), whereas fragments up to 75% of the whole chromosome 5 were found in interchromosomal exchanges. Conclusions: Residual breakpoints after exposure to high-energy iron ions were not distributed randomly along chromosome 5, although the p- and q-arms displayed similar radiosensitivity. Large fragments are either restituted or misrejoined to other chromosome ends, whereas small intrachromosomal fragments can produce either inter- or intrachromosomal exchanges.