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 repai r capabilities of growth-arrested and cycling (stem) 3T3-T cells. In t his 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/m(2)) there was an increase in c-fos and, to a lesser extent, c-jun expression 0.5 h after irradiati on in each 3T3-T phenotype as compared with unirradiated controls. Max imum induction of c-fos was reached at 0.5-1 J/m(2) in TD and growth-a rrested cells, which was 10-fold greater than in stem cells. The induc tion of c-jun in TD and growth-arrested cells reached maximums at 0.5 J/m(2); at this dose each was greater than in stem cells. The increase s in c-fos and c-jun expression were transient in each phenotype reach ing maximums from 0.5 to Ih after irradiation. The expression of type IV collagenase was increased in the non-cycling phenotypes at 2-8 h af ter irradiation. However, collagenase expression was not detected in u nirradiated or irradiated stem cells. These results suggest that growt h arrest, not differentiation or DNA repair capacity, is the primary i nfluence on gene induction after UV irradiation.