FE(II) AND DUST INDUCED CARCINOGENESIS

越来越多的证据表明，过量的肺癌和胃癌 在铁矿石和钢铁厂的工人中发现了癌症。它 已有研究表明，癌症的发病率与接触 空气中的矿物粉尘。然而，负责的活性化合物(S) 所观察到的矿物粉尘的致癌作用尚未确定。 尽管对氧化铁(Fe2O3)颗粒进行了测试，发现 致癌性很小，这可能是由于 水中的氧化铁，即使在pH值稍低的介质中也是如此。亚铁离子，一 在被污染的工业环境中，最丰富的元素是 能够产生活性氧物种(ROS)，并可能起到 在矿物粉尘致癌中起重要作用。由于 铁化学的复杂性及铁诱导细胞的研究现状 转化过程中没有考虑一些重要的化学因素。 例如，Fe(II)氧化为Fe(III)，从而形成ROS 在很大程度上取决于介质的pH值。因为水中的碱性pH 在细胞生长介质中，Fe(II)氧化成Fe(III)在 胞外培养液。因此，短命的ROS是由 Fe(II)和O2的相互作用可能只会损伤细胞膜，从而导致 细胞毒性。相反，当Fe(II)沉积在粒子上时，以及 被细胞吞噬，细胞内释放的Fe(II)可以诱导细胞 转型。这与矿物粉尘引起的 致癌。这项拟议的研究的目的是比较 溶液中Fe(I)离子和含Fe(II)粉尘的致癌作用 不同的铁化合物将在SHE细胞转化实验中进行测试。 进一步确定含铁粉尘的致尘机理 致癌，二氯荧光素将用于评估氧化剂水平 在牢房里。8-oxo-DG和DNA-蛋白质的交联度将被测量到 检测铁化合物对DNA的损伤作用。除了她 细胞，我们还将研究铁化合物对人类的影响 气管上皮(HTE)细胞。此外，我们将比较 氧化应激反应转录因子的反应性，如 作为核因子kB和AP-1对Fe(II)的处理。

Increasing evidence demonstrates that an excess of lung cancer and stomach cancer has been observed in workers of iron ore and steel factories. It has been shown that the incidence of cancer is related to the exposure to airborne mineral dusts. However, the active compound(s) responsible for the observed carcinogenicity of mineral dusts has not yet been identified. Although iron oxide (Fe2O3) particles have been tested and found to produce little carcinogenicity, this was likely due to the insolubility of iron oxide in water, even in a slightly low pH medium. Ferrous ion, one of the most abundant elements in polluted industrial environment, is capable of producing reactive oxygen species (ROS), and may play an important role in mineral dust-induced carcinogenesis. Due to the complexity of iron chemistry, previous studies on iron-induced cell transformation did not take into account some important chemical factors. For example, oxidation of Fe(II) to Fe(III) which results in ROS formation is greatly dependent upon the pH of media. Because of the alkaline pH in cell growth medium, oxidation of Fe(II) to Fe(III) takes place quickly in the extracellular medium. Therefore, the short lived ROS resulting from interaction of Fe(II) and O2 may only damage cell membrane which causes cell toxicity. In contrast, when Fe(II) is deposited on a particle, and phagocytized by cells, the released Fe(II) in cells can induce cell transformation. This is relevant to the mineral dust-induced carcinogenesis. The aims of this proposed research are to compare the carcinogenicity of Fe(I) ions in solution and Fe(II)-containing dusts. Different iron compounds will be tested in SHE cell transformation assay. To further determine the mechanism of Fe(II) containing dust-induced carcinogenesis, dichlorofluorescein will be used to estimate oxidant level in cells. 8-oxo-dG and DNA-protein crosslinkings will be measured to detect the DNA damage induced by iron compounds. In addition to SHE cells, we will also investigate the effect of iron compounds on human tracheal epithelial (HTE) cells. Moreover, we will compare the responsiveness of oxidative stress-responsive transcription factors, such as nuclear factor kB and AP-1 to Fe(II) treatment.