This study confirms previous findings that a Western-style diet produces hyperproliferation of epithelial cells in several organs and that the changes can be prevented by increasing dietary calcium and vitamin D alone.
In this study the effects of a Western-style diet on epithelial cell proliferation in the prostate and bladder of C57BL/6J mice were investigated. The Western-style diet contained increased fat and low calcium and vitamin D, compared with AIN-76A control diet, at levels simulating human Western diets based on nutrient density. After feeding the Western-style and AIN-76A diets for 5 and 16 weeks, mice were infused with bromodeoxyuridine (BrdU) for 72 h using s.c. implanted osmotic pumps. Findings revealed that in bladder epithelium BrdU labeling indices were not significantly different (P > 0.05) between mice on the control and Western-style diets at both time periods. However, significant increases in BrdU labeling indices occurred in epithelial cells of the anterior (P = 0.024) and dorsal (P = 0.049) lobes, but not in the ventral lobe (P = 0.21), of the mouse prostate after feeding the Western-style diet for 16 weeks, compared with mice on the control diet. These findings demonstrate Western-style diet induction of epithelial cell hyperproliferation in anterior and dorsal lobes of the mouse prostate. The findings further suggest that these nutrients may have a role in human prostatic carcinogenesis, since the anterior and dorsal lobes of the mouse prostate are homologous with the human prostate in embryological origin and histological structure and carcinomas induced in rodent models have similar characteristics to those found in human prostatic cancer.
Mammary glands of female C57BL/6J mice were analyzed after they were fed a Western-style diet or control AIN-76A diet. The Western-style diet contained several risk factors found in human diets in geographic regions having increased risk for breast cancer: high fat and phosphate and low calcium and vitamin D. After they were fed these diets for 8, 14, and 20 weeks, mice were sacrificed, and mammary glands were removed for morphometric and radioautographic measurements. Although after the animals were fed the Western-style diet for 8 weeks the number of terminal ducts per mouse mammary gland (NTDMG) was similar in the Western-style and control diet groups, after they were fed the Western-style diet for 14 weeks (p < 0.05) and 20 weeks (p < 0.01) the NTDMG significantly increased compared with the control group. Moreover, there was a significant increase (p < 0.01) in the tritiated thymidine labeling index of mammary terminal ductal epithelial cells after 14 and 20 weeks of Western-style diet administration. Thus the Western-style diet induced increased epithelial cell proliferation and increased NTDMG in female mice when fed during young adult growth and development. The findings raise the possibility that the ingestion of a diet with Western-style fat and phosphate content and with low calcium and vitamin D may induce similar changes during the early development of the human mammary gland.
To aid in identifying the ability of chemopreventive agents to inhibit tumor development, new preclinical in vivo rodent models have recently been developed. Some of the models contain targeted mutations capable of increasing the incidence and progression of neoplastic lesions, whereas in other models dietary nutrients induce preneoplastic lesions in normal mice. These new preclinical models are assisting the analysis of genetic and environmental factors leading to neoplasia, and clinical studies to evaluate the chemopreventive efficacy of specific nutrients and pharmacological agents.
A Western-style diet induced pancreatic epithelial cell hyperproliferation in mice, further suggesting that increased fat content and decreased calcium and vitamin D contribute to the development of pancreatic neoplasms.
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