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

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.

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 microm(-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.

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.

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.