Search research reports:
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.
2011 Project Description
Activities: Experiments have been conducted and analyzed in the area of the project (Dietary Selenium and Carcinogenesis by Environmental Agents). Events: The results of the studies have been presented at an international meeting (Chinese Nutrition Society).
Products: The data have been published in refereed journals.
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).
One of the actions of antioxidants is that they may alter the activity of transcription factors that are known to be activated by oxidative stress, including nuclear factor-kB (NF-kB). We previously found that PB activates NF-kB and that dietary vitamin E is effective in decreasing PB-induced NF-kB DNA binding. We therefore hypothesized that dietary vitamin E influences PB-induced changes in cell proliferation and apoptosis through its action on NF-kB.
NF-kB1 deficient mice (p50-/-) and wild-type B6129 mice were fed a purified diet containing 10 or 250 ppm vitamin E (alpha-tocopherol acetate) for 28 days.At that time, half of the wild-type and half of the p50-/- mice were placed on the same diet with 0.05% PB for 10 days.
Compared to wild-type mice, the p50-/- mice had higher levels of cell proliferation and apoptosis. Cell proliferation was significantly increased by PB, but vitamin E did not affect hepatic cell proliferation. Apoptosis was not changed in mice fed PB, and there was no significant difference in apoptosis between control and high vitamin E treated mice. Thus, vitamin E does not appear to influence cell growth parameters in either wild-type or p50-/- mice.
In another study, we examined the role of dietary glycine and the type of oil used as a vehicle on hepatotoxicity in 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153)-treated or control rats. In the first study, glycine or valine (as control) was fed in an unrefined diet at 5% for the entire study (5 days) to inhibit Kupffer cell activity. PCB-153 (100 or 300 umol/kg) dissolved in medium chain triglyceride (MCT) oil, was injected i.p. two days before euthanasia; the peroxisome proliferator Wy-14,643 was included as a positive control. MCT oil decreased cell proliferation by about 50%. PCB-153 slightly increased hepatic cell proliferation, but dietary glycine did not reduce cell proliferation.
Because of the inhibition of cell proliferation in rats receiving MCT oil compared to rats receiving no injection, we hypothesized that MCT oil may have been inhibiting the hepatocyte proliferation in PCB-153-treated rats. We therefore performed another experiment using three types of oil as a vehicle for PCB-153: MCT oil, corn oil and olive oil. Rats were injected with PCB-153 (300 umol/kg) or one of the vehicles, again two days before euthanasia. MCT oil again decreased the hepatocyte proliferation by about 50%. In rats receiving PCB-153, hepatocyte proliferation was slightly higher than their respective vehicle controls for corn oil and olive oil but not for MCT oil.
These studies show that the oil vehicle is important in cell proliferation after PCB exposure, with MCT oil appearing to be protective.
Li, J., C. Harp, J.C. Tharappel, B.T. Spear, and H.P. Glauert. Effect of vitamin E on hepatic cell proliferation and apoptosis in mice deficient in the p50 subunit of NF-kB after treatment with phenobarbital. Food Chem. Toxicol. 49:2706-2709, 2011.
Bunaciu, R.P., J.C. Tharappel, H.J. Lehmler, E.Y. Lee, L.W. Robertson, G. Bruckner, B.T. Spear, and H.P. Glauert. Role of oil vehicle on hepatic cell proliferation in PCB-treated rats. J. Environ. Pathol. Toxicol. Oncol. 30(4):273-282, 2011.