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An examination of the DNA damaging and repair inhibitory capacity of phorbol myristate acetate in human diploid fibroblasts.

The effects of the tumor promoter, phorbol myristate acetate (TPA) on DNA and DNA repair in human diploid fibroblasts was investigated. TPA induced detectable DNA single-strand breaks at doses as low as 1.3 microM using a sensitive nick-translation assay and at doses as low as 40 microM using alkaline sucrose velocity sedimentation analysis. This report provides the first indication of TPA-induced DNA damage in any cell other than a leucocyte. Experiments utilizing enhancers or inhibitors of active oxygen generation suggest that the DNA damage is related to free radical formation. In addition, we have investigated the effects of TPA on survival following u.v.-irradiation and on removal of pyrimidine dimers from cellular DNA and find no indication of enhancement of u.v. sensitivity or inhibition of normal DNA repair processes in these cells. In fact, TPA treatment enhances colony-forming ability of u.v.-irradiated, but not unirradiated cells.