Abstract
To elucidate the mechanism for the transmissible trait of genomic instability induced by ionizing radiation, we hypothesize that the transmission of genomic instability to the progeny is mediated by an irradiated chromosome, and examine this possibility using the chromosome transfer experiment. In the present study, we transferred a human chromosome 8 exposed to 4 Gy of soft X-rays into unirradiated mouse recipient cells by microcell fusion and examined the numerical and structural changes of the transferred human chromosome in the microcell hybrids detected by fluorescence in situ hybridization (FISH) using a fluorescent probe specific for the whole human chromosome 8. In unstable microcell hybrids, we investigated the instability of telomere and subtelomere of human chromosome 8 by telomere FISH and subtelomere FISH, respectively. A human chromosome 8 was structurally stable in all microcell hybrids examined in case of no irradiation, suggesting that the chromosome transfer itself dose not make the transferred chromosome unstable. In contrast, the irradiated chromosome 8 was unstable and involved in multiple chromosome rearrangements in one of seven microcell hybrids. The telomere FISH analysis indicated that the translocations between an irradiated human chromosome and a mouse chromosome might be formed by reunion of chromosome breaks but not by telomere-telomere fusions. The subtelomere FISH analysis indicated that the subtelomere signals of short arms were lost in 90% of cells and that the subtelomere signals responsible for short and long arms localized on two different chromosomes in 10% cells. These results suggest that the irradiated chromosome has a trait to interact with an unirradiated chromosome and act as a driving force for accelerating instability.
