Influence of DNA repair capacity and cell differentiation on UV-induced gene expression

Terminally differentiated (TD) 3T3-T cells have a reduced capacity to repair ultraviolet (UV)-induced DNA damage, as compared with the repair capabilities of growth-arrested and cycling (stem) 3T3-T cells. In this study UV-induced expression of the immediate early response genes c-fos and c-jun and the secondary response gene type IV collagenase in TD, growth-arrested and stem 3T3-T cells was investigated by northern blot analysis. At each UV dose (0-10 J/m2) there was an increase in c-fos and, to a lesser extent, c-jun expression 0.5 h after irradiation in each 3T3-T phenotype as compared with unirradiated controls. Maximum induction of c-fos was reached at 0.5-1 J/m2 in TD and growth-arrested cells, which was 10-fold greater than in stem cells. The induction of c-jun in TD and growth-arrested cells reached maximums at 0.5 J/m2; at this dose each was greater than in stem cells. The increases in c-fos and c-jun expression were transient in each phenotype reaching maximums from 0.5 to 1 h after irradiation. The expression of type IV collagenase was increased in the non-cycling phenotypes at 2-8 h after irradiation. However, collagenase expression was not detected in unirradiated or irradiated stem cells. These results suggest that growth arrest, not differentiation or DNA repair capacity, is the primary influence on gene induction after UV irradiation.