Reduction of unscheduled DNA synthesis and plasminogen activator activity in Hutchinson-Gilford fibroblasts during passaging in vitro: partial correction by interferon-beta.

Abstract

Two fibroblast cell lines (PG3KT and PG1NA) derived from Hutchinson-Gilford syndrome (progeria) cases were characterized, at various population doubling levels (PDL), with respect to the capacity of ultraviolet light (UV, mainly 254 nm wavelength)-induced unscheduled DNA synthesis (UDS) and plasminogen activator-like protease activity (PA). The UDS levels in PG3KT and PG1NA cells at PDL 2-3 were only slightly less than those in normal fibroblasts. With increasing PDL, both progeria cell lines exhibited reduction of the UDS levels and undetectable ones at PDL 9-11. Prompt and transient induction of PA was also detectable at less than PDL 5, whereas it was undectable at higher PDL. However, the levels of UDS and PA induction were increased about 3-7 times after pretreatment with 100 IU/ml human interferon (HuIFN)-beta preparations for more than 24 h prior to UV irradiation, although UDS and PA were undetectable at more than PDL 10. These results suggest that cytokines such as HuIFN-beta transiently compensate for the decreases in UDS and PA inducibility in progeria cells with aging.