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ABSTRACTWe previously reported hyperproliferation and hyperplasia in C57Bl/6 mouse mammary gland after feeding a Western-style diet (WD); these findings decreased after supplementing WD with increased calcium and vitamin D3. We now again fortified WD with increased calcium and vitamin D3from two sources: (1) a food source, calcium- and vitamin D3-enriched yogurt (WDydiet) or (2) adding calcium and vitamin D3directly to WD (WDCaDdiet). After 6 months of feeding the number of mammary ducts was higher in mice consuming WD compared to WDy(216.0 vs. 202.7, P<.05) and WDCaD(216.0 vs. 194.9, P<.001). The percentage of small ducts increased in WD compared to AIN-76A controls (23.3 vs. 17.4) but was lower in the WDy(17.1) and WDCaD(14.8) groups. WD mice had higher numbers of epithelial cells per duct than WDy(33.2 vs. 27.4, P<.001) and WDCaD(33.2 vs. 27.8, P<.001) mice, and AIN-76A-fed mice had higher numbers than WDy(31.1 vs. 27.4, P<.005) or WDCaD(31.1 vs. 27.8, P<.01) mice. Mitotic index was higher in WD than in WDCaDmice (0.0020 vs. 0.0009, P<.001). Thus, small mammary gland ductules and mitosis increased after feeding WD and decreased after supplementing the diets with increased calcium and vitamin D3, administered either in a dairy food (yogurt) or directly as calcium carbonate plus vitamin D3in WD, suggesting further study of these nutrients for their possible relationship to breast cancer prevention. [ABSTRACT FROM AUTHOR]

Orange peel is a rich source of flavonoids with polymethoxyflavones as major constituents, compounds associated with potential antioxidant, anti-inflammatory, and antitumor activities. We studied the effect of an orange peel extract (OPE) on intestinal tumor growth in ApcMinmice, a mouse model for human familial adenomatous polyposis (FAP). The OPE contained 30 polymethoxyflavones, a mixture that included tangeretin (19.0), heptamethoxyflavone (15.24), tetramethoxyflavone (13.6), nobiletin (12.49), hexamethoxyflavone (11.06), and sinensitin (9.16). ApcMinmice were fed one of four diets (1) AIN-76A control diet; (2) a new Western-style diet (NWD), i.e., AIN-76A diet modified with decreased calcium, vitamin D, and methyl-donor nutrients and increased lipid content); (3) NWD with 0.25 OPE; and (4) NWD with 0.5 OPE, with all additives premixed in the diet. After 9 weeks of feeding NWD to the ApcMinmice, tumors increased mainly in the colon, with tumor multiplicity increasing 5.3-fold and tumor volume increasing 6.7-fold. After feeding 0.5 OPE in NWD, the development of tumors markedly decreased, with multiplicity decreasing 49 in the small intestine and 38 in the colon. NWD also led to increased apoptosis in intestinal tumors, and 0.5 OPE in NWD further increased apoptosis in tumors of the small and large intestine. Findings indicated that OPE inhibited tumorigenesis in this preclinical mouse model of FAP, and increased apoptosis may have contributed to this effect. [ABSTRACT FROM AUTHOR]

We reported previously that a new Western-style diet (NWD) for 18 months, consisting of elevated lipids and decreased calcium, vitamin D and methyl-donor nutrients, induced colonic tumors in normal C57Bl/6 mice [Newmark,H.L. et al. (2001) A Western-style diet induces benign and malignant neoplasms in the colon of normal C57Bl/6 mice. Carcinogenesis, 22, 1871–1875], suggesting a new mouse model for human sporadic colon cancer. Here, we have extended this study during a longer feeding period of 2 years wherein tumor formation, tumor inhibition by addition of dietary calcium and vitamin D and their effects on gene expression were determined. We also similarly tested individual supplements of methyl donor (transfer) nutrients (folic acid, choline, methionine and dietary fiber), but these had no significant effect on colonic tumor incidence or multiplicity, whereas supplementation with combined calcium and vitamin D produced significant decrease in both colon tumor incidence and multiplicity, during 2 years of feeding. No visible colonic tumors were found at 6 months, very few at 12 months, more at 18 months and significantly at 24 months. In a related study of gene changes of the mouse colonic mucosa at 6 months of feeding taken from this study, long before any tumors were visibly detectable, indicated altered profiles of gene expression linked to later risk of dietary initiation of colon tumor formation. This type of early genetic altered profile, an indication of increased risk of later colonic tumor development, may become a useful tool for prediction of colon tumor risk while the colon grossly still appears histologically and physiologically normal. [ABSTRACT FROM AUTHOR]