Extracellular matrix and radiation G1 cell cycle arrest in human fibroblasts

It is thought that sublethal doses of radiation cause cells to pause in either G1 or G2 phase, but that then cells with repaired DNA damage reenter the cell cycle. However, it has been observed that gamma-irradiation causes normal human fibroblasts to arrest indefinitely in G1 phase unless the irradiated cells are subcultured. This indicates that cell adhesion plays a role in maintaining the arrest. We now show that the type of extracellular matrix dramatically affects the percentage of cells that arrest in G1 phase. The prolonged radiation G1 arrest in human fibroblasts has been referred to as "senescence-like"; however, we find that smooth muscle alpha-actin is highly expressed in cells that arrest in G1 phase after irradiation. This indicates that the fibroblasts differentiate to myofibroblasts. Together, our results show that the length of radiation G1 arrest in human fibroblasts is affected by the type of extracellular matrix on which the cells are irradiated and that arrest results in myofibroblast differentiation.