Is delayed genomic instability specifically induced by high-LET particles?

Ionizing radiation can induce a large variety of damages in the DNA. The pr ocessing or repair of this damage occurs in the first minutes up to several hours after irradiation. Afterwhile the remaining lesions are fixed in an irreparable state. However, in recent years, data have accumulated to sugge st that genomic instability can manifest in the progeny of irradiated cells leading to accumulation of damage through cell generations. Different biol ogical endpoints were described: delayed cell death, delayed mutations, de novo chromosomal instability. The question regarding the ability of sparsel y ionizing X-or gamma-rays to induce such phenomenon is still unclear for n ormal cells. In most of the reports, high linear energy transfer (LET) part icles are able to induce genomic instability but not low-LET particles. The mechanisms underlying this phenomenon are still unknown. In human fibrobla sts irradiated by heavy ions in a large range of LETs, we showed that the c hromosomal instability is characterized by telomeric associations (TAS) inv olving specific chromosomes. The same instability is observed during the se nescence process and during the first passages after viral transfection. Th e specific chromosomal instability that we observed after irradiation would not be a direct consequence of irradiation but would be a natural phenomen on occurring after many cell divisions. The effect of the irradiation would lie on the bypass of the senescence process that would permit cells with e nd to end fusions to survive and be transmitted through cell generations, a ccumulating chromosome rearrangements and chromosome imbalances. Research o n molecular mechanisms of chromosomal instability is focused on the role of telomeres in end to end fusions, Such observations could contribute to und erstand why chromosomal instability is not a dose dependant phenomenon. Why high-LET particles would be so potent in inducing delayed instability? The answer might lie in the study of primary effects of ionizing radiations (X-rays, gamma-rays and heavy ions). Cell survival studies showed that K-s hell ionizations could be the primary physical events responsible of cell d eath. The quality of the DNA damages and gene mutations high-LET induced co uld be the keyhole leading to the great efficiency of these particles. (C) 1998 Published by Elsevier Science B.V. All rights reserved.