Aiyar J, Berkovits H J, Floyd R A, Wetterhahn K E
Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755.
Chem Res Toxicol. 1990 Nov-Dec;3(6):595-603. doi: 10.1021/tx00018a016.
The reaction of chromium(VI) with hydrogen peroxide was studied in the presence of glutathione. In vitro, reaction of chromium(VI) with hydrogen peroxide alone led to production of hydroxyl radical as the significant reactive intermediate, while reaction of chromium(VI) with glutathione led to formation of two chromium(V)-glutathione complexes and the glutathione thiyl radical. Incubation of chromium(VI) with glutathione prior to addition of hydrogen peroxide led to formation of peroxochromium(V) species and a dramatic increase in hydroxyl radical production over that detected in the reaction of chromium(VI) with hydrogen peroxide alone. In contrast, addition of chromium(VI) to a preincubated mixture of glutathione and hydrogen peroxide led to a decrease in hydroxyl radical production over that obtained in the reaction of chromium(VI) with hydrogen peroxide. When pBR322 DNA was added to the above reactions, the extent of chromium(VI)-induced DNA strand breakage correlated with the relative amount of hydroxyl radical formed. Reaction of chromium(VI) with calf thymus DNA in the presence of a preincubated mixture of glutathione and hydrogen peroxide led to detection of the 8-hydroxydeoxyguanosine adduct, whose formation correlated with that of hydroxyl radical production. No significant chromium-DNA adduct formation was detected. The results suggest that, in the cellular metabolism of chromium(VI), preformed chromium(V)-glutathione complexes may react with hydrogen peroxide in a Fenton-type manner to produce hydroxyl radical as the DNA-damaging agent. However, if glutathione reacts with hydrogen peroxide prior to exposure to chromium(VI), the amount of hydroxyl radical generated may not be sufficient to cause significant DNA damage.(ABSTRACT TRUNCATED AT 250 WORDS)
在谷胱甘肽存在的情况下，研究了铬（VI）与过氧化氢的反应。在体外，铬（VI）单独与过氧化氢反应会产生作为主要反应中间体的羟基自由基，而铬（VI）与谷胱甘肽反应会形成两种铬（V）-谷胱甘肽络合物和谷胱甘肽硫自由基。在加入过氧化氢之前将铬（VI）与谷胱甘肽一起孵育会导致过氧铬（V）物种的形成，并且与铬（VI）单独与过氧化氢反应相比，羟基自由基的产生显著增加。相反，将铬（VI）添加到预先孵育的谷胱甘肽和过氧化氢混合物中会导致与铬（VI）与过氧化氢反应相比羟基自由基产生减少。当将pBR322 DNA添加到上述反应中时，铬（VI）诱导的DNA链断裂程度与形成的羟基自由基的相对量相关。在预先孵育的谷胱甘肽和过氧化氢混合物存在下，铬（VI）与小牛胸腺DNA反应导致检测到8-羟基脱氧鸟苷加合物，其形成与羟基自由基的产生相关。未检测到明显的铬-DNA加合物形成。结果表明，在铬（VI）的细胞代谢中，预先形成的铬（V）-谷胱甘肽络合物可能以芬顿型方式与过氧化氢反应，产生羟基自由基作为DNA损伤剂。然而，如果谷胱甘肽在暴露于铬（VI）之前与过氧化氢反应，则产生的羟基自由基量可能不足以导致明显的DNA损伤。（摘要截短于250字）
