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Dietary Selenium and Carcinogenesis by Environmental Agents
Department of Human Environmental Sciences
For 2007, it was estimated that 22,850 Kentuckians would develop cancer and that 9,390 would die from it (American Cancer Society 2007). In addition, the death rate from lung cancer in Kentucky is the highest of the 50 states, for both men and women. The major cause of lung cancer is cigarette smoking (American Cancer Society 2007); Kentucky has the highest smoking prevalence in the USA (CDC 2006). Kentuckians are also exposed to PCBs, due to the presence of several Superfund toxic waste sites in the state. Individuals who live or work near Superfund sites may be at higher risk for liver cancer or other types of cancer. This research will show if dietary selenium may prevent the development of lung cancer induced by cigarette smoking and the development of liver cancer induced by PCBs. These results will provide a greater understanding of the role of dietary antioxidants in cancer development and thus can help to provide a mechanistic basis for dietary recommendations for the prevention of cancer. It may be desirable to produce agricultural products with higher amounts of selenium or other dietary antioxidants if this hypothesis is correct.
2009 Project Description
Experiments have been conducted and analyzed in the area of the project (Dietary Selenium and Carcinogenesis by Environmental Agents). The results of one of the studies have been presented at a national meeting, Experimental Biology. The data have been published in two refereed journals (Toxicological Sciences; Archives of Toxicology).
The original objectives of the project were
1) to determine if dietary selenium inhibits lung cancer induced by cigarette smoke in the A/J mouse model;
2) to determine if dietary selenium influences cigarette smoke-induced changes in cytochrome P-450 (CYP) induction, in oxidative stress, and in cell proliferation; and
3) to determine the effect of dietary selenium on the initiating activity of polychlorinated biphenyls (PCBs).
In studies published in the last year, we first examined if dietary selenium could inhibit pulmonary cell proliferation in control and cigarette smoke-exposed female A/J mice. Selenium in the form of sodium selenite was supplemented to purified diets to yield 0.15, 0.5, or 2.0 mg selenium/kg diet. After 3 weeks, mice in each dietary group were divided into two subgroups; one used as control while the other was exposed to cigarette smoke for five consecutive days. Cigarette smoke increased cell proliferation in the terminal bronchioles and large airways, but not in alveoli. High-selenium diets inhibited cell proliferation in the alveoli, terminal bronchioles and large airways areas in both control and smoke-exposed mice. Increasing the dietary selenium level led to the increased selenium levels in the blood and lung, and increased glutathione peroxidase activity in the lung. It is concluded that dietary selenium inhibits pulmonary cell proliferation in both control and cigarette smoke-exposed mice, indicating that selenium is inhibiting cell proliferation independently of smoke exposure, and that this inhibition may be related to selenium concentration and glutathione peroxidase activity in the lung.
In another study we examined if subacute exposure to the perfluorooctanesulfonamide N-ethyl perfluorooctanesulfonamidoethanol (N-EtFOSE), a weak peroxisome proliferator, causes a redox imbalance in vivo. Female Sprague-Dawley rats were treated orally with N-EtFOSE and levels of N-EtFOSE and its metabolites as well as markers of peroxisome proliferation and oxidative stress were assessed in serum, liver and/or uterus. The N-EtFOSE metabolite profile in liver and serum was in good agreement with reported in vitro biotransformation pathways in rats and the metabolite levels decreasing in the order perfluorooctanesulfonate (PFOS) >> perfluorooctanesulfonamide ~ N-ethyl perfluorooctanesulfonamidoacetate >> perfluorooctanesulfonamidoethanol ~ N-EtFOSE. Although N-EtFOSE treatment significantly decreased the growth rate, increased liver weight and activity of superoxide dismutases (SOD) in liver and uterus (total SOD, CuZnSOD and MnSOD), a metabolic study revealed no differences in the metabolome in serum from N-EtFOSE-treated and control animals. Overall, this study demonstrates the biotransformation of N-EtFOSE to PFOS in rats that is accompanied by N-EtFOSE-induced alterations in antioxidant enzyme activity.
These studies have been published and have contributed to an increase in knowledge about environmental chemicals and the effect of nutrition.
Xie, W., Q. Wu, I. Kania-Korwel, J.C. Tharappel, S. Telu, M.C. Coleman, H.P. Glauert, K. Kannan, S.V.S. Mariappan, D.R. Spitz, J. Weydert, H.-J. Lehmler. Subacute exposure to N-ethyl perfluorooctanesulfonamidoethanol results in the formation of perfluorooctanesulfonate and alters superoxide dismutase activity in female rats. Arch. Toxicol. 83:909-924, 2009. DOI 10.1007/s00204-009-0450-y http://dx.doi.org/10.1007/s00204-009-0450-y
Li, J., J.C. Tharappel, S.G. Han, A.H. Cantor, E.Y. Lee, C.G. Gairola, and H.P. Glauert. Effect of dietary selenium and cigarette smoke on pulmonary cell proliferation in mice. Toxicol. Sci., 111:247-253, 2009. http://dx.doi.org/10.1093/toxsci/kfp151