Progress 10/01/01 to 10/19/04
Outputs
1. What major problem or issue is being resolved and how are you resolving it (summarize project aims and objectives)? How serious is the problem? What does it matter? Cancer is the second leading cause of death in the U.S. and causes untold suffering. The National Institute of Health estimates overall annual costs related to cancer at $107 billion for medical expenses and lost productivity. Scientific evidence suggests that up to one-third of the U. S. cancer deaths (over 500,000 in 1999) are related to nutrition and could be prevented. Attaining the project objectives will help to document the role of nutrition as a major modifiable factor for individuals to decrease their cancer risk. Therefore, determining the benefits of certain micronutrients for decreasing cancer risk will help prevent human suffering, save lives, and reduce costs associated with the disease. Substantial evidence indicates that increased consumption of certain micronutrients is associated with
decreased risk of many common cancers. Some micronutrients have shown anti-cancer actions in cell culture and animal model studies. This protection may be due to a number of protective actions, such as antioxidant, anti-inflammatory, detoxification, or cell regulatory effects. However, the evidence from human studies provides associations rather than cause-and-effect links between micronutrient intakes and cancer risk. Therefore, experimental studies which measure the effects of specific dietary or nutrient interventions on human cancer risk are needed. This project focused on reducing the risk of cancer by changing the dietary intake of selected micronutrients, such as selenium, beta-carotene, lycopene and citrus liminoids. Human feeding experiments were conducted to test the efficacy of micronutrient interventions for cancer prevention and to identify surrogate endpoints and putative biomarkers of cancer risk that can be nutritionally modified. Candidate mechanisms by which
micronutrients might prevent cancer are being identified by analyzing their effects on gene expression and on other putative biomarkers of cancer risk. The project focused on the roles of selenium, lycopene, beta-carotene and other phytonutrients of interest in the nutritional prevention of cancer. This project focused on identifying micronutrients in food that protect against cancer in humans and defining the optimum amount and method of intervention for cancer prevention. This research is covered under the ARS Human Nutrition National Program 107 which states that "human nutrition...has moved from a focus on prevention of nutrient deficiencies to an emphasis on health maintenance and reduced risks of chronic diseases," such as cancer. This research focused on the ARS Program Components "research on the role of phytonutrients in the prevention of chronic disease..." and "dietary interventions." Understanding more about the role of phytonutrients in decreasing the risk for cancer
incidence or progression will lead to improved nutrient recommendations for the United States population, as well as providing information relevant to farmers and food producers who seek to insure that the United States food supply is healthful. This project will terminate in early fiscal year 2005. 2. List the milestones (indicators of progress) from your Project Plan. Year 1 (FY 2002) Begin intervention phase of a human selenium supplementation study that will determine whether selenium supplementation has a beneficial impact on health indices relevant to cancer prevention and health status, such as genetic mutations, sperm motility, thyroid hormone status and body composition. Measure antioxidant status and other indices relevant to cancer prevention in healthy people with spinal cord injuries, a historically underserved population. Develop indices and biomarkers for measuring antioxidant status and oxidative damage for use in studies of citrus liminoid, carotenoid, and
phytonutrient metabolism. Year 2 (FY 2003) Complete the intervention phase of the human selenium supplementation study. Begin cell culture studies on selenium regulation of cancer gene expression. With collaboration from scientists in the WHNRC and the University of California, complete data analysis on the bioavailability of citrus liminoids and the impact of cherries on oxidative defense. With collaboration from the Western Regional Research Center of USDA, collect data from a human intervention study using tomatoes rich in cis- and trans-lycopene, a carotenoid believed to help prevent prostate cancer. Year 3 (FY 2004) Complete intervention phase of the lycopene isomer study. Analyze lycopene data. Complete the follow-up phase of the selenium supplementation study. Complete cell culture studies and submit paper on selenium regulation of cancer-related gene expression 3. Milestones: A. The milestones listed below were scheduled to be completed during FY 2004. Complete intervention
phase of the lycopene isomer study. Analyze lycopene data. We completed the intervention phase of the lycopene isomer study, with 22 out of 24 subjects successfully completing the study. We have analyzed lycopene concentrations and finished ancillary measurements, such as cholesterol concentrations and antioxidant status, on all of these studies. We have collected data for the study and begun statistical analysis. We plan to to draft a manuscript on this study by December 2004. Complete the follow-up phase of the selenium supplementation study. This has been substantially completed. Forty-two men completed the intervention phase. The one-year follow-up visits have been completed for all but 4 subjects, whose final visits are scheduled for November 2004. We have completed about one-third of the selenium assays and have just begun the glutathione peroxidase assays in earnest with the help of 2 summer assistants. We have measured mRNA expression patterns in blood of 22 men and are
analyzing that data now. Complete cell culture studies and submit paper on selenium regulation of cancer-related gene expression. We have completed the third and final replication of our mammary cell culture study with Tom Wang at BHNRC. We found 9 out of 34,500 genes that were both regulated by selenium and differentially expressed in tumor cells, including 2 selenoproteins: SEPW1, previously identified as a potential target in our preliminary screening experiment; and GPX4, whose expression in white blood cells was up regulated by high-selenium yeast. We have requested funding to study these candidate targets in NCI grant applications. B. This project is scheduled to be replaced and will be terminated late in FY 2004 or early in FY 2005. 4. What were the most significant accomplishments this past year? A. Because of the recent increase in obesity in healthy adults in the United States and the world, more research is needed to evaluate the impact of micronutrient intake on bodily
functions and the development of chronic diseases. Scientists at the Western Human Nutrition Research Center, Davis, CA, measured selenium status and metabolism in healthy adult men under controlled conditions. Research led to identification of a previously unknown interaction between selenium status, thyroid hormone functions, and body weight. Research is in progress to better elucidate the relationship between selenium status and intake and thyroid function, body weight, and the risk for chronic diseases such as cancer. B. None. C. None. D. None. 5. Describe the major accomplishments over the life of the project, including their predicted or actual impact. We hypothesized that thousands of Americans with severe chronic physical disabilities are at risk for low antioxidant nutrient status, and correspondingly high risk for cancer, because of their typically low energy expenditures and low socioeconomic status. We surveyed nutrient intakes and concentrations in two studies of subjects
with physical disabilities or spinal cord injuries, one in San Francisco and one in Davis, California. Both groups had low intakes of vegetables and citrus fruits, and trends for low intakes of all antioxidant nutrients. Vitamin E, vitamin D and total carotenoid concentrations were low, while vitamin A and individual carotenoids showed non-significant lower trends. Since adequate antioxidant nutrients are associated with decreased cancer risk, nutrition professionals might improve the health of patients with physical disabilities by periodically monitoring their intakes and status of antioxidant nutrients. We determined that anticancer liminoid compounds found in citrus foods are absorbed by humans into the bloodstream and therefore may contribute to systemic cancer protection. We assessed the physiologic effects of cherry consumption on plasma urate, antioxidant and inflammatory markers in 10 healthy women who consumed two large servings of Bing sweet cherries. Plasma urate decreased
after cherry consumption. This supports the reputed anti-gout efficacy of cherries. We used stable and radioisotopes to follow the time-course of the appearance and disappearance of beta-carotene and vitamin A and their metabolites in human blood, in a series of collaborative studies with the University of California Davis. The pattern of appearance and disappearance of these nutrients allowed us to elucidate key features of vitamin A and carotenoid metabolism that impact human nutrient status. For example, our results suggest that at least part of beta-carotene is absorbed by an active process, and that the absorption of beta-carotene and lutein differ in important ways. Insights into these active transport mechanisms should eventually lead to improved estimates of vitamin A and carotenoid status and requirements for individuals, and offer insights into the absorption, metabolism, and utilization of these cancer-delaying phytonutrients. We determined the conversion of beta-carotene
to vitamin A is poorer and more variable than historically assumed. Vitamin A is necessary for normal cell growth and differentiation, and beta-carotene supplies most of the vitamin A for most of the people of the world. Therefore, finding that beta-carotene conversion to vitamin A is less effective than previously believed means that it is a poorer source of this cancer- preventing nutrient than assumed. This has led to recalculating the dietary contribution of plant foods to total vitamin A content in the food supply. We measured selenium absorption, metabolism and excretion under controlled conditions in healthy young adult men, and identified a previously unknown interaction between selenium status and thyroid hormones. Selenium consistently prevents cancer in human trials, but it is not known how it works. We fed healthy men 300 micrograms of selenium per day and--in collaboration with colleagues at the University of California Davis-- measured the expression of the human
genome in white blood cells using DNA microarrays. We obtained the first in-vivo measurements of dietary selenium-regulated gene expression in human white blood cells. These results show that dietary selenium intake can affect cancer risk by altering the expression of genes related to the cancer process. This is one of the first demonstrations that nutritional supplements can change gene expression in humans. We also identified 4 selenium-regulated genes in cultured human mammary cells as new potential targets for nutritional breast cancer prevention. 6. What science and/or technologies have been transferred and to whom? When is the science and/or technology likely to become available to the end- user (industry, farmer, other scientists)? What are the constraints, if known, to the adoption and durability of the technology products? Information on the absorption, metabolism, and functions of selenium, liminoids, and carotenoids, as well as on the conversion of beta-carotene to
vitamin A was published in the "American Journal of Clinical Nutrition" and is available for public use. 7. List your most important publications in the popular press and presentations to organizations and articles written about your work. Burri, B. 2004. Gordon Conference on Carotenoids. January 2004. Ventura, CA. Burri, B. 2004. Carotenoid Bioavailability. Western Regional Section of the American Chemical Society, October 16, 2003. Long Beach, CA. Burri, B. 2004. Carotenoids in Pumpkin, Lycopene Estimates in Food, and the Vitamin Status of Korean Alcoholics. In: Proceeding of the High Performance Liquid Phase Separation. June 2004. Philadelphia, PA. Burri, B. J., Dopler-Nelson, M., and Neidlinger, T. R. 2004. The relative impact of methodological improvements in liquid chromatography and dietary intake measurements on the correlation of dietary and serum lycopene (abstract). In: Proceedings of the High Performance Liquid Phase Separation and Related Techniques. P-0205. Seo, J.
S., Yang, K. M., Kim, J. M., Min, H., Kim, C. S., and Burri, B. J. 2004. Effect of chronic alcohol consumption on plasma cholesterol and antioxidant vitamins in Korean alcoholics (abstract). In: Proceedings of the High Performance Liquid-Phase Separation and Related Techniques. P- 0206. Seo, J. S., Quan, Z., Burri, B. J., Neidlinger, T. R. 2004. Extraction and chromatography of carotenoids from pumpkin powder (abstract). In: Proceedings of the High Performance Liquid Phase Separation and Related Techniques. P-0902.
Impacts
(N/A)
Publications
- Turnlund, J.R., Jacob, R.A., Keen, C.L., Strain, J.J., Kelley, D.S., Domek, J.M., Keyes, W.R., Ensunsa, J.L., Lykkesfeldt, J., Coulter, J. 2004. Long- term high copper intake: effects on indices of copper status, antioxidant status, and immune function in young men. American Journal of Clinical Nutrition. 79:1037-1044.
- Manners, G.D., Jacob, R.A., Breksa III, A.P., Hasegawa, S., Schoch, T.K. 2003. Bioavailability of citrus limonoids in humans. Journal of Agricultural and Food Chemistry, Vol 51, p. 4156-4161.
- Hawkes, W.C., Alkan, F.Z., Oehler, L. 2003. Absorption, distribution and excretion of food selenium in healthy men. Journal of Nutrition. 133:3434- 3442.
- Hawkes, W.C., Keim, N.L. 2003. Dietary selenium intake modulates thyroid hormone and energy metabolism in men. Journal of Nutrition. 133:3443-3448.
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Progress 10/01/02 to 09/30/03
Outputs
1. What major problem or issue is being resolved and how are you resolving it? Substantial evidence indicates that increased consumption of certain micronutrients is associated with decreased risk of many common cancers. Some micronutrients have shown anti-cancer actions in cell culture and animal model studies. This protection may be due to a number of protective actions, such as antioxidant, anti-inflammatory, detoxification, or cell regulatory effects. However, the evidence from human studies provides associations rather than cause-and-effect links between micronutrient intakes and cancer risk. Therefore, experimental studies which measure the effects of specific dietary or nutrient interventions on human cancer risk are needed. This project focuses on reducing the risk of cancer by changing the dietary intake of selected micronutrients. Human feeding experiments will be conducted to test the efficacy of micronutrient interventions for cancer prevention and to
identify surrogate endpoints and putative biomarkers of cancer risk that can be nutritionally modified. Candidate mechanisms by which micronutrients might prevent cancer will be identified by analyzing their effects on gene expression and on other putative biomarkers of cancer risk. The project will focus on the roles of selenium, lycopene, citrus liminoids and other phytonutrients of interest in the nutritional prevention of cancer. 2. How serious is the problem? Why does it matter? Cancer is the second leading cause of death in the U.S. and causes untold suffering. The National Institute of Health estimates overall annual costs related to cancer at $107 billion for medical expenses and lost productivity. Scientific evidence suggests that up to one-third of the U. S. cancer deaths (over 500,000 in 1999) are related to nutrition and could be prevented. Attaining the project objectives will help to document the role of nutrition as a major modifiable factor for individuals to
decrease their cancer risk. Therefore, determining the benefits of certain micronutrients for decreasing cancer risk will help prevent human suffering, save lives, and reduce costs associated with the disease. 3. How does it relate to the National Program(s) and National Program Component(s) to which it has been assigned? The project focuses on identifying micronutrients in food that protect against cancer in humans and defining the optimum amount and method of intervention for cancer prevention. This research is covered under the ARS Human Nutrition National Program 107 which states that "human nutrition...has moved from a focus on prevention of nutrient deficiencies to an emphasis on health maintenance and reduced risks of chronic diseases," such as cancer. This research focuses on the ARS Program Components "research on the role of phytonutrients in the prevention of chronic disease..." and "dietary interventions." 4. What were the most significant accomplishments this past year?
A. Over 250 thousand people in the United States have severe spinal cord injuries that restrict their access to foods, yet there is almost no research on the nutritional status or nutrient requirements for these people. With the collaboration of the Paralyzed Veterans of America, we measured the dietary intakes and serum concentrations of a variety of micronutrients such as vitamins A, C, D and E in healthy adults with spinal cord injuries and other physical disabilities living in Northern California. We found that healthy people with spinal cord injuries, as a group, had very low intakes and serum concentrations of vitamins D, E, and some carotenoids. Vitamin D is essential for good bone health, vitamin E is an important antioxidant, and all these nutrients appear to reduce the risk of cancer, so identifying these deficits is an essential first step in improving the nutritional health and well-being of this population. B. Determined the effect of moderate antioxidant intake on
biomarkers of oxidant damage in healthy men whose typical diet contained few fruits and vegetables (average of 2.6 servings per day). The 39 nonsmokers and 38 smokers were given a daily supplement (272 mg vitamin C, 31 mg vitamin E, and 400 micro g folic acid), or placebo, for 90 d with their usual diet. Supplementation increased plasma vitamins C and E, but had no effect on the oxidant biomarkers. This means that in healthy young men, a modest intake of dietary antioxidants is adequate to minimize oxidative damage. C. Target populations, small farmers: No activities to report. D. None. 5. Describe the major accomplishments over the life of the project, including their predicted or actual impact. We hypothesized that thousands of Americans with severe chronic physical disabilities are at risk for low antioxidant nutrient status, and correspondingly high risk for cancer, because of their typically low energy expenditures and low socioeconomic status. We surveyed nutrient intakes
and concentrations in two studies of subjects with physical disabilities or spinal cord injuries one in San Francisco and one in Davis, California. Both groups had low intakes of vegetables and citrus fruits, and trends for low intakes of all antioxidant nutrients. Vitamin E, vitamin D and total carotenoid concentrations were low, while vitamin A and individual carotenoids showed non-significant lower trends. Since adequate antioxidant nutrients are associated with decreased cancer risk, nutrition professionals might improve the health of patients with physical disabilities by periodically monitoring their intakes and status of antioxidant nutrients. We obtained the first in-vivo measurements of dietary selenium-regulated gene expression in human white blood cells. These results show that dietary selenium intake can affect cancer risk by altering the expression of genes related to the cancer process. We determined that anticancer liminoid compounds found in citrus foods are
absorbed by humans into the bloodstream and therefore may contribute to systemic cancer protection. We assessed the physiologic effects of cherry consumption on plasma urate, antioxidant and inflammatory markers in 10 healthy women who consumed two large servings of Bing sweet cherries. Plasma urate decreased after cherry consumption. This supports the reputed anti-gout efficacy of cherries. We determined the conversion of beta-carotene to vitamin A is poorer and more variable than historically assumed. Vitamin A is necessary for normal cell growth and differentiation, and beta-carotene supplies most of the vitamin A for most of the people of the world. Therefore, finding that beta-carotene conversion to vitamin A is poorer than expected means that beta-carotene is a poorer source of this cancer related nutrient than assumed. Identified 4 selenium-regulated genes in cultured human mammary cells as new potential targets for nutritional breast cancer prevention. 6. What do you
expect to accomplish, year by year, over the next 3 years? This project will close midyear FY2004. During 2004 Complete the intervention phase of the lycopene isomer study. Analyze lycopene data. Complete the follow-up phase of the selenium supplementation study. Complete cell culture studies and submit paper on selenium regulation of cancer-related gene expression 8. List your most important publications in the popular press and presentations to organizations and articles written about your work. (NOTE: This does not replace your peer-reviewed publications listed below). Burri, B. J., Chan, M., Dopler-Nelson, M., and Neidlinger, T. R. Serum concentrations of vitamin D and antioxidant vitamins in healthy people with spinal cord injuries. FASEB 2003. 17:180.7.
Impacts
(N/A)
Publications
- Burri, B. J., and Neidlinger, T. R. Dietary intakes and serum concentrations of vitamin E and total Carotenoids of healthy people with severe physical disabilities are lower than matched controls. Journal of American Dietetic Association. 2002. 102: 1804-1806.
- Burri, B. J., Dopler-Nelson, M., and Neidlinger, T. R. Measurements of the major isoforms of vitamins A and E and Carotenoids in the blood of people with spinal-cord injuries. Journal of Chromatography. 2003. A. 987:359-366.
- Jacob, R. A., Spinozzi, G. M., Simon, V. A., Kelley, D. S., Prior, R. L. Hess-Pierce, B. and Kader, A. A. Consumption of cherries lowers plasma urate in healthy women. Journal of Nutrition. 2003. 133:1826-1829.
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Progress 10/01/01 to 09/30/02
Outputs
1. What major problem or issue is being resolved and how are you resolving it? Substantial evidence indicates that increased consumption of certain micronutrients is associated with decreased risk of many common cancers. Some micronutrients have shown anti-cancer actions in cell culture and animal model studies. This protection may be due to a number of protective actions, such as antioxidant, anti-inflammatory, detoxification, or cell regulatory effects. However, the existing evidence from human studies provides associations rather than cause-and- effect links between micronutrient intakes and cancer risk. Therefore, experimental studies which measure the effects of specific dietary or nutrient interventions on human cancer risk are needed. This project will focus on reducing the risk of cancer by changing the dietary intake of selected micronutrients. Human feeding experiments will be conducted to test the efficacy of micronutrient interventions for cancer
prevention and to identify intermediate biomarkers of cancer risk that can be nutritionally modified. Candidate mechanisms by which micronutrients might prevent cancer will be identified by analyzing their effects on gene expression and on other intermediate biomarkers of cancer risk. The project will focus on the roles of selenium, lycopene, antioxidant status, citrus limonoids, and other phytochemicals in the nutritional prevention of cancer. 2. How serious is the problem? Why does it matter? Cancer is the second leading cause of death in the U.S. and causes untold suffering. The National Institute of Health estimates overall annual costs related to cancer at $107 billion for medical expenses and lost productivity. Scientific evidence suggests that up to one-third of the U. S. cancer deaths (over 500,000 in 1999) are related to nutrition and could be prevented. Attaining the project objectives will help to document the role of nutrition as a major modifiable factor for
individuals to decrease their cancer risk. Therefore, determining the benefits of certain micronutrients for decreasing cancer risk will help prevent human suffering, save lives, and reduce costs associated with the disease. 3. How does it relate to the national Program(s) and National Program Component(s) to which it has been assigned? The project focuses on identifying micronutrients in food that protect against cancer in humans and defining the optimum amount and method of intervention for cancer prevention. This research is covered under the ARS Human Nutrition National Program 107 which states that "human nutrition...has moved from a focus on prevention of nutrient deficiencies to an emphasis on health maintenance and reduced risks of chronic diseases," such as cancer. This research focuses on the ARS Program Components "research ?on the role of phytonutrients in the prevention of chronic disease..." and "dietary interventions." 4. What was your most significant accomplishment
this past year? A. Selenium is the only nutrient that consistently prevents cancer in human trials, but it is not known how it works. We fed healthy men 300 micrograms of selenium/day as high-selenium yeast at WHNRC and Dr. Jeff Gregg in the Department of Pathology at UC Davis School of Medicine measured the effects on expression of 12,625 genes in white blood cells using DNA microarrays. We found that selenium supplementation changed the expression of several hundred genes, many associated with cancer. This is the first demonstration that nutritional supplements can change gene expression in humans. B. Citrus limonoids have shown anticancer activity in animal models, but it is not known if they are taken up into the blood and tissues by humans. To determine the bioavailability of citrus limonoids in humans we analyzed the blood of healthy adults after they consumed pure doses of the prominent limonoid found in orange juice, limonin glucoside. Analysis of the blood showed the
appearance of limonin in the plasma at 1, 3, 6, and 24 hr after the dose. These results show for the first time that limonoids in citrus are absorbed systemically by humans and therefore may contribute to anticancer protection of body tissues. We studied the effects of genetic variability on vitamin A and beta- carotene metabolism to begin to determine the genetic basis of an individual's requirement for these nutrients. Our experiments with genetically altered mice have shown only small genetic effects on vitamin A metabolism. The results suggest that there might be multiple mechanisms for lipid and vitamin A metabolism, minimizing the effects of genetic variations. Nutritional genomics ? how nutrition affects gene expression and how genetics affects nutrient metabolism - is a new science with great promise for unraveling nutrient mechanisms and for individualized dietary recommendations. WHNRC formed partnerships with Children's Hospital Oakland Research Institute and with the UC
Davis Cancer Center. We submitted separate multi-million dollar center grant applications to NIH to use nutritional genomics to study minority health disparities and the nutritional prevention of cancer, respectively. Given UC Davis' commitment to a campus-wide genomics theme, including the soon-to-be- completed 200,000 square foot Genomics and Biomedical Sciences Facility, these collaborations will grow into major research projects and into national centers of excellence if either of the grants is funded. C. None, however, our research is broad-based and provides necessary background for research that benefits targeted populations. D. For in-house projects: See sections 4A. and 4B above, and ARIS entries for Project 5306- 51530-010-00D. For Subordinate projects: This report serves to document progress for the subordinate project Micronutrients Modulation of Oxidant Damage (CRIS # 5306-51530-010-05S) conducted under a Specific Cooperative Agreement between the WHNRC and the USDA
ARS Human Nutrition Research Center on Aging at Tufts University. The link between high fruit/vegetable intake and reduced chronic disease may be partly explained by antioxidants in fruits and vegetables such as vitamins C and E. To determine the effect of moderate antioxidant intake on oxidant damage to the body, we measured oxidant damage to body fat and protein in 77 healthy men whose typical diet contained few fruits and vegetables (2.7 servings/day). The men, age 20-50 y, were given a daily antioxidant supplement containing vitamins C and E, or a look-alike placebo pill. Blood and urine was taken at the beginning and end of the 3 month study to see if the supplement treatment reduced the amount of oxidant damage to body fats and proteins. The supplementation increased blood vitamin C and E levels, but had no effect on the oxidant damage measures. Therefore, in healthy young men, the body's internal antioxidant defense system and a modest amount of dietary antioxidants is
apparently adequate to prevent levels of body oxidant damage that can be measured by current methods. This report serves to document progress for the subordinate project Antioxidant Nutrient Status of Children from Tibet (CRIS # 5306-51530-010- 06S) conducted under a Specific Cooperative Agreement between the WHNRC and the University of California Berkeley. The people of Tibet have adapted to life at high altitudes over centuries. Their diet appears to be unique, and to contain few sources of carotenoids and vitamin C. The effect of their unusual diet and lifestyle on antioxidants and phytonutrient cancer preventative status is not known. In collaboration with Terma, we collected blood samples from pre-school children from Tibet, and analyzed them for the antioxidant nutrients A, E, and the carotenoids. We also analyzed for vitamin D. Our most interesting findings are the extremely low vitamin D and carotenoid concentrations of these children. Their low vitamin D status may be
responsible for the high incidence of rickets in this population. 5. Describe your major accomplishments over the life of the project, including their predicted or actual impact? Obtained the first in-vivo measurements of dietary selenium-regulated gene expression in human white blood cells. The results show that dietary selenium intake can affect cancer risk by altering the expression of genes related to the cancer process. Determined that anticancer limonoid compounds found in citrus foods are absorbed by humans into the bloodstream and therefore may contribute to systemic anticancer protection. Determined that the conversion of beta-carotene to vitamin A is poorer and more variable than historically assumed. These results indicate that public health programs using beta-carotene rich foods to correct vitamin A deficiency are not likely to be fully successful. 6. What do you expect to accomplish, year by year, over the next 3 years? During FY 2003: Complete the intervention phase
of the selenium supplementation study. Begin a pilot study on cancer prevention with selenium. Begin cell culture study of selenium regulation of cancer gene expression. Submit papers on the effects of selenium supplementation on gene expression. With collaborators at the UC Davis Department of Pomology: complete data analysis and reports for studies on the effect of fruit consumption on antioxidant protection. With collaborators at the USDA ARS Western Regional Research Center: complete data analysis and reports for study of the bioavailability of citrus limonoids. With the collaboration of the Western Regional Research Center of USDA collect, analyze, and process specific genetic varieties of tomatoes that are high in different forms of lycopene, a carotenoid that is believed to prevent prostate cancer. Begin the intervention phase of the lycopene isomer study to determine whether tangerine tomatoes have lycopene isomers that are more bioavailable than standard tomatoes. With the
collaboration of the Western Regional Research Center of USDA complete plans for an intervention study of the effect of stabilized rice bran on biomarkers of cancer and heart disease risk. During FY2004: Complete the follow-up phase of the selenium supplementation study. Complete cell culture studies and submit paper on selenium regulation of cancer-related gene expression. Complete the intervention phase of the lycopene isomer study. Analyze lycopene data. With collaborators at the University of California Davis Department of Nutrition finalize plans for a study of the effect of fat concentration and composition on carotenoid metabolism. Begin the intervention study of the effect of stabilized rice bran on biomarkers of cancer and heart disease risk. During FY2005: Compete pilot study on cancer prevention with selenium. Begin the study of the effect of fat concentration and composition on carotenoid metabolism. Analyze the results from the study on the effect of stabilized rice bran
on biomarkers of cancer and heart disease risk. 8. List your most important publications and presentations, and articles written about your work (NOTE: this does not replace your review publications which are listed below) Wood, M. Selenium's secrets probed in new study. Agricultural Research. 2002. 50(3). P. 8-9. Hawkes, C.W. Presented information on Nutrition and Cancer to: (1) the Mather VA Medical Center Prostate Cancer Support Group, June 28, 2002, Sacramento CA; and (2) the African-American Prostate Cancer Initiative at Antioch Progressive Baptist Church, August 15, 2002, Sacramento CA. Jacob, R., Sotoudeh, G., Aiello, G., Prior, R., Hess-Pierce, B. Kader, A. Assessing Antioxidant Capacity of Fruits and Their Physiologic Effect. California Institute of Food and Agricultural Research, Conference XV, December 11, 2001, Napa CA. Burri, B. J., Neidlinger, T. R. Conversion of beta-carotene to vitamin A measured with stable isotope methods. National Audio Video, Inc., Denver.
Proceedings of Nutrition Week 2002. Trace Elements/vitamins/supplements. Tape 80:S226. Dopler-Nelson, M., Burri, B. J. Dietary intake in the spinal cord injured patient. National Audio Video, Inc., Denver. Proceedings of Nutrition Week 2002. Cardiovascular. Tape 102:S318.
Impacts
(N/A)
Publications
- Burri, B. J. Lycopene and human health, in Phytonutrients in health and disease, Meskin, M. S., Bidlack, W. R., Davies, A. J., and Omaye, S. T., eds. CRCPress; Boca Raton, Chapter 11. 2002. p. 157-172.
- Hickenbottom, S., Deuker, S. R., Burri, B. J., Lin, Y. M., Neidlinger, T. R., Clifford, A. J. Variability of conversion of beta-carotene to vitamin A in men as measured by using a double-isotope tracer design. American Journal of Clinical Nutrition. 2002. v. 75. p. 900-907.
- Buhman, K. K., Smith, S. J., Stone, S. J , Repa, J. J., Wong, J. S., Knapp, F. F. Jr., Burri, B., J., Hamilton, R. L., Abumrad, N. A., Farese, R. V. Jr. DGAT1 is not essential for intestinal triacylglycerol absorption or chylomicron synthesis. Journal of Biological Chemistry. 2002. v. 277. p. 25474-25479.
- Burri, B. J., Dopler-Nelson, M. A., Neidlinger, T. R. Metabolism of beta- carotene and vitamin A measured with stable isotope methods. Western Regional American Chemical Society. 2002. Abstract A31.
- Dopler-Nelson, M., Burri, B. J., Neidlinger, T. R. Dietary intakes and nutrient status in the spinal cord injured patient. Western Regional American Chemical Society. 2002. Abstract A32.
- Burri, B. J., Neidlinger, T.R. Conversion of beta-carotene to vitamin A measured with stable isotope methods. Nutrition Week. 2002. Abstract A226.
- Dopler-Nelson, M., Burri, B.J.. Dietary intake in the spinal cord injured patient. Nutrition Week. 2002. Abstract A318.
- Burri, B. J., Neidlinger, T.R., Clifford, A.J., Hickenbottom, S.A., Deuker, S. Beta-carotene absorption: small versus moderate doses. International Carotenoid Symposium 13. 2002. Abstract 104.
- Hawkes, W.C. The biological effects of dietary selenium in humans: Can selenium supplementation decrease risk of chronic diseases? In: Schrauzer GN, editor. Salt Lake City, UT. Institut Rosell Lallemand and International Association of Bioinorganic Scientists. 2002. p 32-42.
- Jacob, R. A. Niacin, In: Present Knowledge in Nutrition, 8th Edition, Bowman, B.A. and Russell, R.M., Eds., Washington, D.C. ILSI Press; Chapter 19. 2001. p. 199-206.
- Jacob, R.A., Sotoudeh, G. Vitamin C function and status in chronic disease. Nutrition in Clinical Care. 2002. v. 5. p. 66-74.
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