RADIATION-INDUCED CHROMOSOMAL INSTABILITY IN HUMAN T-LYMPHOCYTES

Chromosomal instability in proliferating mammalian cells is characteri zed by a persistent increase of chromosomal aberrations and rearrangem ents occurring de novo during successive cell generations. Recent resu lts from many laboratories using a variety of cells and cytogenetic en d points show that this phenotype can be induced by low as well as hig h LET irradiation. A typical feature of chromosomal instability in pri mary human G(0)-lymphocytes exposed to gamma-irradiation at both high dose rate (45 Gy h(-1)) and low dose rate (0.024 Gy h(-1)) is the appe arance of novel aberrations in the clonal progeny of the irradiated ce ll, many generations after the exposure. The same phenotype was observ ed in lymphocytes that were allowed to recover for 5 days in G(0) afte r the radiation exposure, as well as in hprt-mutant T cell clones. The se results demonstrate that neither the acute genotoxic stress caused by high dose rate as compared to low dose rate irradiation, nor a hypo thesized conflict between mitogen induced growth stimulation and growt h arrest due to radiation damage, seem to be critical conditions for t he development chromosomal instability in these cells. In contrast to observations in other cells, no evidence of a persistent decrease of c loning ability was observed in the progeny of radiation-exposed human lymphocytes, and no alteration was observed in their sensitivity to a second radiation exposure. Furthermore, the frequency of CA-repeat len gth variation at three loci was not increased in the progeny of X-irra diated T cells as compared to non-irradiated cells, which indicates th at microsatellite instability is not part of the chromosomal instabili ty phenotype in human T-lymphocytes. (C) 1998 Elsevier Science B.V. Al l rights reserved.