Interrelation amongst differentiation, senescence and genetic instability in long-term cultures of fibroblasts exposed to different radiation qualities.

The goal of the present study was to investigate aging and genetic instability in the progeny of human fibroblasts exposed to X-rays and carbon ions.Following irradiation, cells were regularly subcultured until senescence. At selected time-points BrdU-labelling index, expression of cell cycle related proteins, cell differentiation pattern and chromosome aberrations were assessed.After exposure, an immediate cell cycle arrest occurred followed by a period of a few weeks where premature differentiation and senescence were observed. In all cultures cycling cells expressing low levels of cell cycle inhibiting proteins were present and finally dominated the populations. About 5months after exposure, the cellular and molecular changes attributed to differentiation and senescence reappeared and persisted. Concurrently, genetic instability was observed, but the aberration yields and types differed between repeated experiments. The descendants of cells exposed to carbon ions did not senesce earlier and displayed a similar rate of genetic instability as the X-ray progeny. For high doses an impaired cell cycle regulation and extended life span was observed, but finally cell proliferation ceased in all populations.The descendants of irradiated fibroblasts undergo stepwise senescence and differentiation. Genetic instability is frequent and an extension of the life span may occur