Huang X, Zhuang Z, Frenkel K, Klein C B, Costa M
Nelson Institute of Environmental Medicine, New York University Medical Center, New York.
Environ Health Perspect. 1994 Sep;102 Suppl 3(Suppl 3):281-4. doi: 10.1289/ehp.94102s3281.
Increasing evidence demonstrates the reactive oxygen species (ROS) are implicated in metal carcinogenesis. Exposure of cultured Chinese hamster ovary (CHO) cells to several nickel compounds, i.e. NiS, Ni3S2, NiO (black and green), and NiCl2 has been shown to increase oxidation of 2',7-dichlorofluorescein to the fluorescent 2',7-dichlorofluorescein (DCF), suggesting that nickel compounds increased the concentration of oxidants in CHO cells. This fluorescence can be attenuated by addition of exogenous catalase to the extracellular media, indicating that H2O2 is one of the formed oxidants in this system. Fluorimetric measurements of chromogens following thiobarbituric acid reaction showed that nickel compounds also induce lipid peroxidation with a decreasing potency NiS, Ni3S2 > black NiO > green NiO > NiCl2. These results suggest that lipid hydroperoxides may also be produced through the action of nickel in intact cells. MgCl2, an antagonist of Ni-induced DNA strand breaks and cell transformation, has no effect on the formation of DCF fluorescence induced in CHO cells by nickel. The results suggest that nickel is an active inducer of ROS in intact mammalian cells and that the molecular mechanism of nickel carcinogenesis may involve multiple steps of nickel-mediated ROS.
越来越多的证据表明，活性氧（ROS）与金属致癌作用有关。已证明，将培养的中国仓鼠卵巢（CHO）细胞暴露于几种镍化合物，即硫化镍（NiS）、三硫化二镍（Ni3S2）、氧化镍（黑色和绿色）以及氯化镍中，会使2',7-二氯荧光素氧化为荧光性的2',7-二氯荧光素（DCF），这表明镍化合物增加了CHO细胞中氧化剂的浓度。向细胞外培养基中添加外源性过氧化氢酶可减弱这种荧光，这表明H2O2是该系统中生成的氧化剂之一。硫代巴比妥酸反应后对发色团进行荧光测定表明，镍化合物还会诱导脂质过氧化，其效力顺序为NiS、Ni3S2＞黑色NiO＞绿色NiO＞NiCl2。这些结果表明，脂质氢过氧化物也可能通过镍在完整细胞中的作用而产生。MgCl2是镍诱导的DNA链断裂和细胞转化的拮抗剂，对镍在CHO细胞中诱导产生的DCF荧光的形成没有影响。结果表明，镍是完整哺乳动物细胞中ROS的活性诱导剂，镍致癌的分子机制可能涉及镍介导的ROS的多个步骤。
