The Chemical-Induced Genotoxicity of Depleted Uranium

描述(申请人提供)：铀已开采多年，用于制造核反应堆的燃料以及制造原子武器、弹药和装甲的材料。铀的放射性与肺癌、肾癌和白血病的发生有关。人们对铀的直接化学遗传毒性知之甚少。这项研究的目的是收集更多关于铀的化学遗传毒性的信息。总的目的是(1)确定铀的化学毒性诱导的可能机制，(2)研究贫铀(醋酸铀酰)诱导HBE-16细胞基因表达改变的化学效应，以及(3)确定改变的基因在铀致癌中的作用。利用基因芯片在体外分析铀转化细胞的基因表达，将提供哪些基因正在被改变的图像，并提出关于可能的致癌机制的问题。据推测，铀将改变负责细胞凋亡和癌基因诱导的基因。了解铀与DNA的反应对于更好地了解这种致癌物是如何致癌的，并有助于阐明接触铀的人患肺癌和其他癌症的机制是重要的。

DESCRIPTION (provided by applicant): Uranium has been mined for many years and used for fuel for nuclear reactors and materials for atomic weapons, ammunition, and armor. The radioactivity of uranium has been linked to the development of lung, kidney cancers, and leukemia. Little is known about the direct chemical genotoxicity of uranium. The purpose of the research is to gather more information about the chemical genotoxicity of uranium. The overall aims are to (1) identify the possible mechanisms induced by the chemical toxicity of uranium, (2) investigate the chemical effects of altered gene expression in HBE-16 cells, induced by exposure to depleted uranium as uranyl acetate, and (3) to determine the role of the altered genes in uranium carcinogenesis. The use of cDNA microarray to profile the gene expression of uranium-transformed cells in vitro will provide a picture as to what genes are being altered and pose questions regarding possible mechanisms of carcinogenesis. It is hypothesized that uranium will alter genes responsible for apoptosis and oncogene induction. Understanding how uranium reacts with DNA is important to better understand how this carcinogen induces cancer and to help to elucidate mechanisms of lung and other cancers in people exposed to uranium.