Gao M, Binks S P, Chipman J K, Levy L S
Institute of Occupational Health, University of Birmingham, Edgbaston, UK.
Toxicology. 1993 Jan 29;77(1-2):171-80. doi: 10.1016/0300-483x(93)90147-k.
Rat hepatocytes were used to investigate the possible induction of unscheduled DNA synthesis (UDS) and the extent of DNA strand breaks induced by sodium dichromate (a representative chromium(VI) compound) and chromium acetate hydroxide (chromium(III)) in vitro. Cytotoxicity, measured using tetrazolium salt (MTT) reduction assay, was found at a much higher dose of chromium(III), (> 50 microM), compared to that of chromium(VI), (> 2.5 microM), in cultured hepatocytes over 20 h treatment at 37 degrees C. Chromium(VI), but not chromium(III), stimulated minimal UDS in hepatocytes at sub-cytotoxic concentrations. A positive UDS response was only observed at cytotoxic concentration. DNA strand breaks in hepatocytes were induced by chromium(VI) following incubation at 37 degrees C for 1 h at doses of 10, 20 and 40 microM sodium dichromate. The subsequent ligation of such strand breaks in hepatocytes treated with 40 microM chromium(VI) for 1 h at 37 degrees C was demonstrated. The majority of strand breaks was repaired within 30 min following removal of the chromate. In conclusion, chromate-induced DNA strand breakage, possibly involving the formation of oxygen radicals and lack of significant UDS have some analogy to those produced by ionizing radiation.
采用大鼠肝细胞研究了重铬酸钠（一种代表性的六价铬化合物）和氢氧化铬乙酸盐（三价铬）在体外诱导非程序性DNA合成（UDS）的可能性以及诱导DNA链断裂的程度。在37℃下对培养的肝细胞进行20小时处理后，使用四唑盐（MTT）还原试验测定细胞毒性，结果发现，与六价铬（>2.5 microM）相比，三价铬（>50 microM）在更高剂量时才具有细胞毒性。在亚细胞毒性浓度下，六价铬而非三价铬可刺激肝细胞产生最小程度的UDS。仅在细胞毒性浓度下观察到阳性UDS反应。在37℃下用10、20和40 microM重铬酸钠孵育1小时后，六价铬可诱导肝细胞中的DNA链断裂。结果表明，在37℃下用40 microM六价铬处理肝细胞1小时后，随后这些链断裂会发生连接。在去除铬酸盐后，大多数链断裂在30分钟内得到修复。总之，铬酸盐诱导的DNA链断裂可能涉及氧自由基的形成，且缺乏明显UDS，这与电离辐射产生的情况有一些相似之处。
