Abstract-Solid tumors show areas of differential blood supply due to decreasing vascularisation from periphery towards the core. As a result, a gradient of oxygen is formed such that internal areas with low oxygen tension lead to altered physiochemical conditions. This state of low oxygen-called hypoxia-is gaining interest due to a large scale shift in metabolism of the tumor cells. Reactive Oxygen Species (ROS) thus produced cause extensive DNA damage in hypoxic core regions, exacerbating the aggressiveness of cancer by accumulation of mutations. We show how the ubiquitous cellular enzyme Catalase may prevent ROS mediated damage through chelation of metal ions. Metal ions are known to increase oxidative stress in a cell and recent reports implicated involvement of metal ions in controlling p53 function. We propose that chelation therapy in solid tumors can delay the accumulation of mutations by catalase mediated decrease in ROS levels and by rescuing the p53 activity in a cell.Index Terms-Catalase, chelation, hypoxia, oxidative stress. I. INTRODUCTIONCancer is a multigenic process which involves the accumulation of several mutations which offer a competitive advantage to the cancerous cell over normal cells. The accumulation of mutations in the DNA relate to the pathogenesis of the disease. However, a number of cellular mechanisms-called cell cycle checkpoints-ensure that an abnormal cell does not proceed towards cell division either by forcing these cells into cell-cycle arrest or apoptosis [1]. Multiple mutations are thus required to transform a normal cell into a cancer cell that increase the cancer's clinical aggressiveness-that is conversion from the relatively innocuous benign tumors to debilitating metastatic cancers. Also, a loss of heterozygocity (LOH) [2] is seen in cancers which impair both alleles of genes which otherwise show normal phenotype in heterozygous state.Solid tumors are cancerous growths in the form of sarcomas, carcinomas and lymphomas that contain an abnormal mass of tissue devoid of liquid area [3]. Rapid proliferation of cells that form the tumor cause internal areas to be poorly vascularized [4]. The low blood supply established to internal areas of the tumor causes a shortage of various nutrients including oxygen. The decrease in oxygen supply from about 2.5-9 percent oxygen tension to less than 1 percent is called hypoxia [5]. As oxygen is critical for cellular energetics, hypoxia is reported to alter metabolic state of a cell and hence a marked level of oxidative stress is seen due Cells possess several enzymes that utilize the ROS species as substrates and form products that are harmless to the cell. The various enzymes include catalase, superoxide dismutase and glutathione. Our study involves the use of the enzyme catalase. Catalase catalyses the breakdown of hydrogen peroxide to water and molecular oxygen. This enzyme has one of the highest turnover number in that it catalyses the breakdown of millions of substrate molecules to products per second [8]. This activity is critica...
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