Role of active oxygen species in metal-induced DNA strand breakage in human diploid fibroblasts

The ability of 6 metal salts to induce DNA damage in human diploid fibroblasts was examined. Cadmium, magnesium, manganese, chromium(VI), zinc and selenite were all shown to induce DNA strand breaks as measured by two independent assays. DNA strand breaks were repaired within 2-4 h after removal of metal and this repair appeared not to be sensitive to "long-patch" repair inhibitors. With the exception of selenite, metal-induced DNA damage appeared to be mediated via the formation of active oxygen species since oxygen scavengers when administered simultaneously with the metal, antagonized strand break formation. Selenite-induced DNA damage (as previously reported) was dependent on the formation of a selenite-glutathione conjugant and was not affected by oxygen radical scavengers. Scavenger treatment did not enhance cloning ability of metal-treated cells suggesting that DNA strand breaks may not be important in metal-induced cytotoxicity.