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Carcinogenesis Advance Access published online on November 18, 2008
Carcinogenesis, doi:10.1093/carcin/bgn229
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Harold Newmark1,4, Kan Yang2, Naoto Kurihara2, Kunhua Fan2, Leonard Augenlicht3 and Martin Lipkin2

1 Laboratory for Cancer Research, Rutgers University, Piscataway, NJ
2 Strang Cancer Research Laboratory, New York, NY
3 Albert Einstein College of Medicine, Bronx, NY

4 Correspondence to Dr. Harold L. Newmark, 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, Email address: Harold L. Newmark – pnewmark{at}comcast.net

We previously reported that a 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 [1], 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, while 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, 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.

Key Words: Western diet • C57Bl/6 mice • Calcium and vitamin D • Methyl donors • Sporadic colon cancer

Received June 6, 2008; revised September 22, 2008; accepted September 24, 2008.


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