Reaction of chromium(VI) with glutathione or with hydrogen peroxide: identification of reactive intermediates and their role in chromium(VI)-induced DNA damage.
Reaction of chromium(VI) with glutathione or with hydrogen peroxide: identification of reactive intermediates and their role in chromium(VI)-induced DNA damage.
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DOI：
10.1289/ehp.919253
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发表时间：
1991-05
影响因子：
10.4
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中科院分区：
文献类型：
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谷胱甘肽或过氧化氢还原铬（VI）和由此产生的DNA损伤后产生的活性中间体的类型已被确定。在体外，铬（VI）与谷胱甘肽的反应导致形成两个铬（V）络合物和谷胱甘肽巯基自由基。当铬（VI）在谷胱甘肽的存在下与DNA反应时，得到铬-DNA加合物，没有DNA链断裂。铬-DNA加合物形成的水平与铬（V）形成相关。铬（VI）与过氧化氢反应导致羟基自由基的形成。在24摄氏度（297 K）时检测不到铬（V）;然而，在77 K时检测到低水平的四过氧铬（V）络合物。在过氧化氢存在下，铬（VI）与DNA的反应产生显着的DNA链断裂和8-羟基脱氧鸟苷加合物，其形成与羟基自由基的产生相关。未检测到显著的铬-DNA加合物形成。因此，铬（VI）诱导的DNA损伤的性质似乎取决于铬（VI）还原过程中产生的反应性中间体，即铬（V）或羟基自由基。
The types of reactive intermediates generated upon reduction of chromium(VI) by glutathione or hydrogen peroxide and the resulting DNA damage have been determined. In vitro, reaction of chromium(VI) with glutathione led to formation of two chromium(V) complexes and the glutathione thiyl radical. When chromium(VI) was reacted with DNA in the presence of glutathione, chromium-DNA adducts were obtained, with no DNA strand breakage. The level of chromium-DNA adduct formation correlated with chromium(V) formation. Reaction of chromium(VI) with hydrogen peroxide led to formation of hydroxyl radical. No chromium(V) was detectable at 24 degrees C (297 K); however, low levels of the tetraperoxochromium(V) complex were detected at 77 K. Reaction of chromium(VI) with DNA in the presence of hydrogen peroxide produced significant DNA strand breakage and the 8-hydroxydeoxyguanosine adduct, whose formation correlated with hydroxyl radical production. No significant chromium-DNA adduct formation was detected. Thus, the nature of chromium(VI)-induced DNA damage appears to be dependent on the reactive intermediates, i.e. chromium(V) or hydroxyl radical, produced during the reduction of chromium(VI).