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Extracellular Matrix and Radiation G₁ Cell Cycle Arrest in Human Fibroblasts¹

Life Sciences Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545

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 -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 -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.

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