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


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 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.


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.
Horstmann
M
M
Department of Genetics, University of Duisburg-Essen, Universitätsstr. 5, D-45117 Essen, Germany.
Durante
M
M
Obe
G
G
D019457:Chromosome Breakage; D007446:Chromosome Inversion; D002895:Chromosomes, Human, Pair 5 / Q000528:radiation effects*; D005260:Female; D020450:Heavy Ions / Q000009:adverse effects*; D006801:Humans; D066298:In Vitro Techniques; D007501:Iron / Q000009:adverse effects*; D008214:Lymphocytes / Q000528:radiation effects; D017384:Sequence Deletion / Q000528:radiation effects; D014178:Translocation, Genetic / Q000528:radiation effects
D007501:Iron