Rossi S C, Gorman N, Wetterhahn K E
Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755.
Chem Res Toxicol. 1988 Mar-Apr;1(2):101-7. doi: 10.1021/tx00002a003.
Incubation of chromate with isolated rat liver mitochondria in vitro resulted in the uptake and reduction of chromium(VI), as well as the formation of chromium(V) species. Chromate was rapidly taken up and reduced by intact mitochondria. The rate of reduction of chromate by intact mitochondria was increased upon addition of succinate or malate plus glutamate, substrates for the electron-transport chain, but was decreased upon addition of cyanide, an inhibitor of the electron-transport chain. Incubation of chromate with mitochondria in the presence or absence of malate, glutamate, and succinate resulted in a steady increase in the level of chromium(V) over time. The extent of chromium(V) formation was increased upon addition of malate, glutamate, and succinate but was inhibited upon addition of the electron-transport chain inhibitors, antimycin, cyanide, or rotenone, to whole mitochondria. High levels of glutamate plus malate inhibited chromium(V) formation; however, high concentrations of succinate or sulfate had no effect. These studies suggest that the chromate-reductase activity in mitochondria is due to the electron-transport chain as well as other mitochondrial reducing systems which are insensitive to inhibitors of the electron-transport chain. Since chromium(VI) is effectively metabolized by mitochondria in vitro and chromium(V) "reactive intermediates" are formed in the process, mitochondria may play a role in chromium(VI) carcinogenesis.
在体外将铬酸盐与分离的大鼠肝线粒体一起温育，导致铬（VI）的摄取和还原，以及铬（V）物种的形成。完整的线粒体能够迅速摄取并还原铬酸盐。添加琥珀酸或苹果酸加谷氨酸（电子传递链的底物）后，完整线粒体还原铬酸盐的速率增加，但添加电子传递链抑制剂氰化物后，该速率降低。在有或没有苹果酸、谷氨酸和琥珀酸存在的情况下，将铬酸盐与线粒体一起温育，会导致铬（V）水平随时间稳步增加。添加苹果酸、谷氨酸和琥珀酸后，铬（V）的形成程度增加，但向整个线粒体中添加电子传递链抑制剂抗霉素、氰化物或鱼藤酮后，铬（V）的形成受到抑制。高浓度的谷氨酸加苹果酸抑制铬（V）的形成；然而，高浓度的琥珀酸或硫酸盐没有影响。这些研究表明，线粒体中的铬酸盐还原酶活性归因于电子传递链以及其他对电子传递链抑制剂不敏感的线粒体还原系统。由于铬（VI）在体外能被线粒体有效代谢，并且在此过程中会形成铬（V）“反应中间体”，因此线粒体可能在铬（VI）致癌过程中发挥作用。
