DIFFERENTIAL INVOLVEMENT OF CHROMOSOME-1 AND CHROMOSOME-4 IN THE FORMATION OF CHROMOSOMAL-ABERRATIONS IN HUMAN-LYMPHOCYTES AFTER X-IRRADIATION

Whole brood samples from two healthy donors were cultured in the prese nce of 5-bromo-2'deoxyuridine (BrdU) for a total of 107 h following in vitro X-irradiation with a dose of 2 Gy. Starting from 35 h after cul ture initiation, every subsequent 12 h a sample was taken from each cu lture and grown in the presence of demecolcine for another 12 h. At ea ch sampling time, the aberrations involving chromosomes 1 and 4 were a nalysed using dual-colour fluorescence in situ hybridization (FISH) wi th chromosome-specific DNA libraries. Following differential staining of sister chromatids, the analysed cells were identified to be either in their first, second or third etc. mitosis after irradiation. Cells within the same postirradiation division contained higher frequencies of aberrations when derived from later sampling times, indicating a de lay in progression of aberrant cells to mitosis. In contrast, when the aberration frequencies are calculated by sampling time (i.e. independ ent of the cell cycle) minimal effect of sampling time could be seen. This observation held true for all types of chromosomal aberrations. A nalysis of about 2250 first-division cells for each donor (derived fro m all sampling times) indicates a relative overrepresentation of chrom osome 4 in the formation of exchange aberrations/colour junctions. Whe reas dicentric frequencies for chromosomes 1 and 4 were close to the e xpected values based on the DNA content of these chromosomes, frequenc ies of reciprocal translocations showed a clear overinvolvement of chr omosome 4. This resulted in a distinct difference in the reciprocal tr anslocation to dicentric ratio, being 1 12 for chromosome 1 and 2.09 f or chromosome 4. These results indicate a non-DNA-proportional distrib ution of radiation-induced chromosome rearrangements in cultured human lymphocytes.