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

Abstract

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 µm⁻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.