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OpenSource Diets-
Creating a Clean Background for Oncology Research
by Matthew R. Ricci, Ph.D. VP, Science Director, Research Diets, Inc. and
Michael A. Pellizzon, Ph.D. Senior Scientist, Research Diets, Inc.
Laboratory animal models are important tools in oncology research, as they allow scientists to test their in vitro-generated hypotheses in a mammalian, whole-animal system. Since many types of cancer can be affected by environmental factors, having control over these factors is key to generating reproducible, meaningful data.
Research Diets products are routinely used for oncology research. OpenSource diets contain purified ingredients provide a clean background (i.e. phytoestrogen and cholorphyll-free) to reduce ‘noise’ during in vivo imaging, and easily control for factors that may impact gene expression.
Effects of Phytoestrogens in Grain-based Diets on Cancer and Related Endpoints
Grain-based chow diets contain ingredients possessing biologically active compounds that can alter the cancer phenotype. One class of compounds called phytoestrogens, which are found in soybean meal and alfalfa, have all been shown to impact cancer endpoints (5, 6) and the concentration of these compounds in chow can have meaningful biological effects on cancer and other phenotypes (1, 10). Since the level of these compounds can vary from one lot to the next by as much as 3 – 6 fold (10), it is possible that they can mask the influence of experimental compounds.
Genistein is a soy-based phytoestrogen that is commonly found in grain-based chow diets, and its influence on cancer is thought to be mediated by its ability to bind estrogen receptors (3, 7). Its potential impact on cancer (i.e. carcinogenic or anticarcinogenic) is related to factors including the dose, age, mode of cancer induction, and rodent model being studied (7). For example, one study suggested that exposure to genistein early in life (i.e. gestational and lactational phases) dose-dependently reduced tumor formation in a carcinogen-induced mammary cancer rat model (11). In contrast, another study showed that dietary genistein dose-dependently increased mammary tumor area in an estrogen-sensitive ovariectomized mouse model.
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various treatments or genetic mutations influence gene expression. Furthermore, the potential for unknown compounds in grains used in chows may have further impact on phenotype, which may translate to the gene level.
Effects on In Vivo Imaging
Finally, the presence of chlorophyll in ingredients of chows such as alfalfa can create background ‘noise’ in studies where imaging technology is used. Therefore, it is essential to use chlorophyll-free diets when such technology is used. >more
OpenSource Diets
OpenSource purified ingredient diets are a solution to these issues, as they do not contain phytoestrogens or chlorophyll. While the lack of these compounds makes purified diets important tools for oncology research, the very nature of OpenSource purified diets argues for their use in all lab animal research. Contact our Resource Center to learn more.
Scientific Litereature References
1. Brown, NM and Setchell,KDR. Animal Models Impacted by Phytoestrogens in Commercial Chow: Implications for Pathways Influenced by Hormones. Laboratory Investigation; 81(5):735-747, 2001.
2. Tovar-Palacio C, Potter SM, Hafermann JC, and Shay NF. Intake of soy protein and soy protein extracts influences lipid metabolism and hepatic gene expression in gerbils. J Nutr. 128:839–842. 1997.
3. Dalu A, Haskell JF, Coward L, and Lamartiniere CA. Genistein, a component of soy, inhibits the expression of the EGF and ErbB2/Neu receptors in the rat dorsolateral prostate. Prostate 37:36–43, 1998.
4. Si, H and Liu, D. Genistein, a Soy Phytoestrogen, Upregulates the Expression of Human Endothelial Nitric Oxide Synthase and Lowers Blood Pressure in Spontaneously Hypertensive Rats. J. Nutr. 138: 297–304, 2008.
5. Zhou, JR, Gugger,ET, Tanaka, T, Guo,Y, Blackburn, GL and Clinton, SK. Soybean Phytochemicals Inhibit the Growth of Transplantable Human Prostate Carcinoma and Tumor Angiogenesis in Mice. J. Nutr. 129:1628–1635, 1999.
6. Javid, SH, Moran, AE, Carothers, AM, Redston, M and Bertagnolli, MM. Modulation of tumor formation and intestinal cell migration by estrogens in the ApcMin/+ mouse model of colorectal cancer. Carcinogenesis. 26 (3):587--595, 2005.
7. Liao, Z, Wang, S, Wiegers,BS and Clinton,SK. Energy Balance Alters Dunning R3327-HProstate Tumor Architecture ,Androgen Receptor Expression, and Nuclear Morphometryin Rats. Prostate, 1-9, 2006.
8. Clinton, SK, Mulloy, AL, Li, SP, Mangian, HJ and Visek, WJ. Dietary Fat and Protein Intake Differ in Modulation of Prostate Tumor Growth, Prolactin Secretion and Metabolism, and Prostate Gland Prolactin Binding Capacity in Rats. J. Nutr. 127: 225–237, 1997.
9. C.D. Kozul, A.P. Nomikos, T.H. Hampton, L.A. Warnke, J.A. Gosse, J.C. Davey, J.E. Thorpe, B.P. Jackson, M.A. Ihnat, J.W. Hamilton, Laboratory Diet Profoundly Alters Gene Expression and Confounds Genomic Analysis in Mouse Liver and Lung, Chemico-Biological Interactions (2007), doi:10.1016/j.cbi.2008.02.008.
10. Thigpen, JE, Setchell, KDR, Saunders,HE, Haseman,JK, Grant, MG and
Forsythe, DB. Selecting the Appropriate Rodent Diet for Endocrine Disruptor Research and Testing Studies. ILAR Journal; 45(4):401-416, 2004.
11. Fritz WA, Coward L, Wang J, and Lamartiniere CA. Dietary genistein: Perinatal mammary cancer prevention, bioavailability and toxicity testing in the rat. Carcinogenesis 19:2151–2158, 1998.
12. Herman,CT et al. Soybean Phytoestrogen Intake and Cancer Risk. J. Nutr. 125:757S-770S, 1995. |
