Frequent involvement of visible chromosomal deletion in X-ray-induced mutants at the HLA-A locus in human T-lymphocytes.

Mutant T-lymphocytes at the HLA-A locus were isolated using a recently developed flow-cytometric assay either immediately after drawing blood (in vivo mutants) or after X-irradiation in vitro. Mutants were subsequently propagated clonally for cytogenetic and molecular analyses. Among the 38 in vivo mutants, none contained an abnormal chromosome 6 on which the HLA-A locus resides (6p21.3). In contrast, mutants recovered after in vitro irradiation frequently carried abnormalities in the short arm of chromosome 6: 11/19 and 5/5 independent mutants for the 1-Gy and 2-Gy groups, respectively. Characteristically, the majority of the aberrations were deletions, commonly involving chromosome 6p21-p23. Because chromosomal deletions involving the selected gene are rare among radiation-induced mutants at the hypoxanthine phosphoribosyltransferase (chromosome X) and thymidine kinase (chromosome 17) loci, the HLA-A locus can be considered as highly prone to chromosomal deletions after radiation exposure. It is generally believed that ionizing radiation randomly breaks DNA, and the higher frequency of chromosomal deletions at the HLA-A locus is unlikely to be due to preferential induction but more likely to the better survivability of the deletion-bearing mutants. Consequently, the results suggest that the human genome is quite heterogeneous with regard to the survivability of cells bearing a chromosomal deletion including different loci.