Evaluation of putative inhibitors of DNA excision repair in cultured human cells by the rapid nick translation assay.
A human fibroblast nick translation assay has been applied to an examination of 48 diverse chemical agents to assess their ability to specifically interfere with the DNA excision-repair process following ultraviolet irradiation. Certain inhibitors of DNA polymerase, ribonucleotide reductase and purine and pyrimidine biosynthesis are shown to inhibit the resynthesis step of repair while DNA intercalators and inhibitors of DNA topoisomerases appear to inhibit the incision step. A variety of other agents previously implicated as inhibitors of DNA repair was also examined and found to have no such effect. This type of analysis should prove useful in the rapid identification of new classes of compounds that antagonize normal cellular repair functions and that might, therefore, act as comutagens or cocarcinogens.
D002478:Cells, Cultured; D004256:DNA Polymerase I / Q000037:antagonists & inhibitors; D004260:DNA Repair / Q000187:drug effects*; D004926:Escherichia coli / Q000201:enzymology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007364:Intercalating Agents / Q000633:toxicity; D009153:Mutagens; D011687:Purines / Q000096:biosynthesis; D011743:Pyrimidines / Q000096:biosynthesis; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D059004:Topoisomerase I Inhibitors; D014466:Ultraviolet Rays
D007364:Intercalating Agents; D009153:Mutagens; D011687:Purines; D011743:Pyrimidines; D059004:Topoisomerase I Inhibitors; D012264:Ribonucleotide Reductases; D004256:DNA Polymerase I