UV-DNA DAMAGE IN MOUSE AND HUMAN-CELLS INDUCES THE EXPRESSION OF TUMOR-NECROSIS-FACTOR-ALPHA

Ultraviolet light induces the expression of tumor necrosis factor alph a (TNF alpha) in many mammalian cells. We have examined the signal for this induction in a human DNA repair-deficient cell line carrying a t ransgene composed of the murine TNF regulatory sequences fused to the chloramphenicol acetyltransferase (CAT) structural gene. When compared by fluence, UVC was a more efficient inducer of CAT than was UVB, but they were equivalent inducers when compared by the frequency of cyclo butyl pyrimidine dimers produced by each source. Further, treatment of UV-irradiated cells with the prokaryotic DNA repair enzyme T4 endonuc lease V increased the level of repair of dimers and concomitantly redu ced CAT gene expression. Membrane-bound TNF alpha expression was incre ased by UV and reduced by repair of dimers. Finally, in the TNFcat tra nsgene system, DNA damage directly to the cell with the transgene was required as cocultivation of unirradiated TNFcat cells with W-irradiat ed cells did not increase CAT activity. These results show that DNA da mage is a signal for the induction of TNF alpha gene expression in mou se and human cells.