Carcinogenesis Advance Access originally published online on November 18, 2008
Carcinogenesis 2009 30(1):88-92; doi:10.1093/carcin/bgn229
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Western-style diet-induced colonic tumors and their modulation by calcium and vitamin D in C57Bl/6 mice: a preclinical model for human sporadic colon cancer
Department of Chemical Biology, Laboratory for Cancer Research, Rutgers University, Piscataway, NJ 08854, USA
1 Department of Experimental Pathology
2 Department of Medicine, Strang Cancer Research Laboratory, New York, NY 10021, USA
3 Department of Surgery, School of Medicine, Keio University, Tokyo 176-8530, Japan
4 Department of Oncology, Albert Einstein College of Medicine, Bronx, NY 10467, USA
* To whom correspondence should be addressed. Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854-8020, USA. Tel: 732-445-3400 ext.229; Fax: 732-445-0687; Email: pnewmark{at}comcast.net
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.
Abbreviations: GI, gastrointestinal; NWD, new Western-style diet; NWD/CaD, new Western-style diet with increased calcium and vitamin D; NWD/Chln, new Western-style diet with increased choline; NWD/FA, new Western-style diet with increased folic acid; NWD/Fb, new Western-style diet with increased fiber; NWD/Methn, new Western-style diet with increased methionine
Received June 6, 2008; revised September 22, 2008; accepted September 24, 2008.
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