Research Accomplishment Reports 2010

Dietary Selenium and Carcinogenesis by Environmental Agents

H.P. Glauert
Department of Human Environmental Sciences

 

Non-Technical Summary

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.

2010 Project Description

Experiments have been conducted and analyzed in the area of the project (Dietary Selenium and Carcinogenesis by Environmental Agents). The results of the studies have been presented at national meetings (Experimental Biology and Society of Toxicology). The data have been published in refereed journals.

2010 Impact

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), activator protein-1 (AP-1), and hypoxia-inducible factor (HIF). Studies were therefore undertaken to examine if cigarette smoke could activate these transcription factors, as well as other transcription factors that may be important in lung carcinogenesis; future studies could then examine if antioxidants inhibited activation of these transcription factors by cigarette smoke.

Female A/J mice were exposed to cigarette smoke for 2, 5, 10, 15, 20, 42, or 56 days (6 hr/day, 5 days/wk). Cigarette smoke did not increase NF-kB activation at any of these times, but NF-kB DNA binding activity was lower after 15 days and 56 days of smoke exposure. The DNA binding activity of AP-1 was lower after 10 days and 56 days but was not changed after 42 days of smoke exposure. The DNA binding activity of HIF was quantitatively increased after 42 days of smoke exposure but decreased after 56 days. Whether the activation of other transcription factors in the lung could be altered after exposure to cigarette smoke was next studied. The DNA binding activities of the forkhead transcription factor FoxF2, myc common factor 1 (myc-CF1), retinoic acid receptor-related orphan receptor (RORE), and p53 were examined after 10 days of smoke exposure. The DNA binding activities of FoxF2 and p53 were quantitatively increased, but those of myc-CF1 and RORE were unaffected.

These studies show that cigarette smoke exposure leads to quantitative increases in DNA binding activities of FoxF2 and p53, while the activations of NF-kB, AP-1, and HIF are largely unaffected or reduced. Since the activities of the oxidative stress-sensitive transcription factors were not affected by cigarette smoke, it is doubtful if dietary antioxidants can counteract the deleterious effects of cigarette smoke by altering the activities of these transcription factors.

2010 Publications

Tharappel, J.C., J. Cholewa, P. Espandiari, B.T. Spear, C.G. Gairola, and H.P. Glauert. Effects of cigarette smoke on the activation of oxidative stress-related transcription factors in female A/J mouse lung. J. Toxicol. Environ. Health, Part A 73:1288-1297, 2010.

Glauert, H.P., K. Calfee-Mason, D.N. Stemm, J.C. Tharappel, and B.T. Spear. Dietary antioxidants in the prevention of hepatocarcinogenesis: a review. Molec. Nutr. Food Res. 54: 875-896, 2010.