Repair of chromate-induced DNA damage in chick embryo hepatocytes.
The repair of DNA damage caused by chromate was examined in chick embryo hepatocytes. Treatment of chick embryo hepatocytes with 5 microM sodium chromate for 2 h caused the formation of DNA strand breaks, DNA interstrand cross-links, and DNA-protein cross-links. The maximal level of strand breaks and DNA interstrand cross-links was observed immediately after the 2 h chromate treatment. After removal of the chromate, strand breaks and DNA interstrand cross-links were completely repaired by 3 h and 12 h, respectively. In contrast, DNA-protein cross-links continued to form reaching a maximal level 3 h after chromate removal. Although the level of DNA-protein cross-links decreased at later times, a significant level persisted 40 h after chromate removal. The effect of these persistent DNA-protein cross-links on gene expression was examined by measuring induction of porphyrin accumulation by propylisopropylacetamide and deferoxamine methanesulphonate, a process known to depend on mRNA synthesis. Induction of porphyrin accumulation was decreased immediately following the 2 h chromate treatment. Only partial recovery of induction was observed even 40 h after chromate removal. The effect of chromate treatment on cellular glutathione levels was monitored. No change in cellular glutathione was observed after a 2 h treatment with 5 microM sodium chromate; however, a three-fold increase was observed 12 h after removal of chromate.
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D002840:Chromates / Q000633:toxicity*; D004247:DNA / Q000378:metabolism; D004260:DNA Repair; D005978:Glutathione / Q000032:analysis; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D011166:Porphyrins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism
D002840:Chromates; D011166:Porphyrins; D011506:Proteins; D004247:DNA; D005978:Glutathione