CLONAL CHROMOSOME-ABERRATIONS AND GENOMIC INSTABILITY IN X-IRRADIATED HUMAN T-LYMPHOCYTE CULTURES

To study the effects of X-irradiation on clone forming ability and karyotypic abnormalities in human peripheral blood lymphocytes, cells were exposed to 3 Gy of X-rays in vitro and either individual T-cell clones or long-term T-cell cultures were established. The karyotypes were analyzed in G-banded chromosome preparations after proliferation for 9-34 days in vitro. T-cell clonal karyotype abnormalities were found in 24 of 37 (65%) irradiated and in two of 43 (5%) control clones. Balanced reciprocal translocations and deletions were the predominating types of clonal aberrations. Complex aberrations and unstable karyotypes were found in about half of the irradiated clones. Some of the T-cell clones demonstrated sequential change from normal to aberrant karyotype. Other clones seemed to develop multiple, heterogeneous chromosomal aberrations during growth in vitro. X-Irradiated T-cells grown in long-term T-cell culture displayed karyotype abnormalities in 60-80% of the cells, and the types of aberrations were similar to those found in the individual, irradiated T-cell clones. An increasing number of cells with the same abnormal karyotype was observed when the cultivation time was extended, indicating clonal proliferation. These results demonstrate that a surprisingly high proportion of T-cells with stable and often complex irradiation-induced chromosome aberrations are able to proliferate and form expanding cell clones in vitro. Furthermore, the results indicate that X-irradiation induces latent chromosome damage and genomic instability in human T-lymphocytes.