Cupo D Y, Wetterhahn K E
Carcinogenesis. 1984 Dec;5(12):1705-8. doi: 10.1093/carcin/5.12.1705.
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.
在鸡胚肝细胞中研究了铬酸盐所致DNA损伤的修复情况。用5微摩尔/升铬酸钠处理鸡胚肝细胞2小时，会导致DNA链断裂、DNA链间交联和DNA - 蛋白质交联的形成。在铬酸盐处理2小时后立即观察到链断裂和DNA链间交联的最高水平。去除铬酸盐后，链断裂和DNA链间交联分别在3小时和12小时完全修复。相比之下，DNA - 蛋白质交联继续形成，在去除铬酸盐后3小时达到最高水平。尽管DNA - 蛋白质交联水平在随后的时间里有所下降，但在去除铬酸盐40小时后仍有显著水平存在。通过测量丙基异丙基乙酰胺和去铁胺甲磺酸盐诱导的卟啉积累来研究这些持续的DNA - 蛋白质交联对基因表达的影响，卟啉积累过程已知依赖于mRNA合成。在铬酸盐处理2小时后，卟啉积累的诱导立即下降。即使在去除铬酸盐40小时后，也仅观察到诱导的部分恢复。监测了铬酸盐处理对细胞谷胱甘肽水平的影响。用5微摩尔/升铬酸钠处理2小时后，未观察到细胞谷胱甘肽的变化；然而，在去除铬酸盐12小时后观察到其增加了三倍。
