Reference SummaryNewmark HL, Carcinogenesis 2009 Jan;30(1):88-92

Title

 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.

Authors

 Newmark HL; Yang K; Kurihara N; Fan K; Augenlicht LH; Lipkin M

Journal

 Carcinogenesis

Volume

 30

Issue

 1

Year

 2009

Pages

 88-92

Abstract

 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.

Links

 J:145013 – MGI References
19017685 – National Library of Medicine/PubMed

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
C57BL/6J Blood vessel tumor
  • (see notes regarding diet)
 (Unspecified organ)

observed
C57BL/6J Intestine - Large Intestine - Cecum adenoma - flat
  • (see notes regarding diet)
 Intestine - Large Intestine - Cecum

observed
C57BL/6J Intestine - Large Intestine - Colon adenocarcinoma
  • (see notes regarding diet)
 Intestine - Large Intestine - Colon

observed
C57BL/6J Intestine - Large Intestine - Colon tumor
  • AIN-76A
 Intestine - Large Intestine - Colon

0 - 6.67
C57BL/6J Intestine - Large Intestine - Colon tumor
  • New western diet (NWD) TD.96096
 Intestine - Large Intestine - Colon

0 - 26.67
C57BL/6J Intestine - Large Intestine - Colon tumor
  • New western diet (NWD) TD.96096
  • vitamin D3 (1alpha,25-(OH)2-D3) (VD3)
  • Calcium-enriched
 Intestine - Large Intestine - Colon

0 - 4.55
C57BL/6J Intestine - Large Intestine - Colon tumor
  • New western diet (NWD) TD.96096
  • Folic acid-enriched
 Intestine - Large Intestine - Colon

0 - 27.78
C57BL/6J Intestine - Large Intestine - Colon tumor
  • choline-enriched
  • New western diet (NWD) TD.96096
 Intestine - Large Intestine - Colon

5.56 - 10
C57BL/6J Intestine - Large Intestine - Colon tumor
  • methionine-enriched
  • New western diet (NWD) TD.96096
 Intestine - Large Intestine - Colon

11.11 - 18.75
C57BL/6J Intestine - Large Intestine - Colon tumor
  • New western diet (NWD) TD.96096
  • high fiber
 Intestine - Large Intestine - Colon

0 - 29.41
C57BL/6J Intestine - Small Intestine adenocarcinoma
  • (see notes regarding diet)
 Intestine - Small Intestine

observed
C57BL/6J Intestine - Small Intestine adenoma - tubular
  • (see notes regarding diet)
 Intestine - Small Intestine

observed
C57BL/6J Intestine - Small Intestine tumor
  • (see notes regarding diet)
 Intestine - Small Intestine

observed
C57BL/6J Intestine - Small Intestine tumor
  • AIN-76A
 Intestine - Small Intestine

0 - 26.67
C57BL/6J Intestine - Small Intestine tumor
  • New western diet (NWD) TD.96096
 Intestine - Small Intestine

0 - 26.67
C57BL/6J Intestine - Small Intestine tumor
  • New western diet (NWD) TD.96096
  • vitamin D3 (1alpha,25-(OH)2-D3) (VD3)
  • Calcium-enriched
 Intestine - Small Intestine

5.56 - 15.38
C57BL/6J Intestine - Small Intestine tumor
  • New western diet (NWD) TD.96096
  • Folic acid-enriched
 Intestine - Small Intestine

7.14 - 26.09
C57BL/6J Intestine - Small Intestine tumor
  • choline-enriched
  • New western diet (NWD) TD.96096
 Intestine - Small Intestine

10 - 33.33
C57BL/6J Intestine - Small Intestine tumor
  • methionine-enriched
  • New western diet (NWD) TD.96096
 Intestine - Small Intestine

11.11 - 25
C57BL/6J Intestine - Small Intestine tumor
  • New western diet (NWD) TD.96096
  • high fiber
 Intestine - Small Intestine

0 - 11.76
C57BL/6J Intestine adenocarcinoma
  • (see notes regarding diet)
 Intestine

observed
C57BL/6J Intestine adenoma
  • (see notes regarding diet)
 Intestine

observed
C57BL/6J Intestine adenoma
  • AIN-76A
 Intestine

observed
C57BL/6J Intestine adenoma
  • New western diet (NWD) TD.96096
 Intestine

observed
C57BL/6J Intestine adenoma
  • New western diet (NWD) TD.96096
  • vitamin D3 (1alpha,25-(OH)2-D3) (VD3)
  • Calcium-enriched
 Intestine

observed
C57BL/6J Intestine adenoma
  • New western diet (NWD) TD.96096
  • Folic acid-enriched
 Intestine

observed
C57BL/6J Intestine adenoma
  • choline-enriched
  • New western diet (NWD) TD.96096
 Intestine

observed
C57BL/6J Intestine adenoma
  • methionine-enriched
  • New western diet (NWD) TD.96096
 Intestine

observed
C57BL/6J Intestine adenoma
  • New western diet (NWD) TD.96096
  • high fiber
 Intestine

observed
C57BL/6J Intestine adenoma - tubular
  • (see notes regarding diet)
 Intestine

observed
C57BL/6J Intestine carcinoma
  • AIN-76A
 Intestine

observed
C57BL/6J Intestine carcinoma
  • New western diet (NWD) TD.96096
 Intestine

observed
C57BL/6J Intestine carcinoma
  • New western diet (NWD) TD.96096
  • vitamin D3 (1alpha,25-(OH)2-D3) (VD3)
  • Calcium-enriched
 Intestine

observed
C57BL/6J Intestine carcinoma
  • New western diet (NWD) TD.96096
  • Folic acid-enriched
 Intestine

observed
C57BL/6J Intestine carcinoma
  • choline-enriched
  • New western diet (NWD) TD.96096
 Intestine

observed
C57BL/6J Intestine carcinoma
  • methionine-enriched
  • New western diet (NWD) TD.96096
 Intestine

observed
C57BL/6J Intestine carcinoma
  • New western diet (NWD) TD.96096
  • high fiber
 Intestine

observed
C57BL/6J Intestine carcinoma - invasive
  • (see notes regarding diet)
 Intestine

observed
C57BL/6J Intestine carcinoma - invasive
  • AIN-76A
 Intestine

0
C57BL/6J Intestine carcinoma - invasive
  • methionine-enriched
  • New western diet (NWD) TD.96096
 Intestine

observed
C57BL/6J Intestine carcinoma - invasive
  • New western diet (NWD) TD.96096
  • high fiber
 Intestine

2
C57BL/6J Intestine carcinoma - invasive
  • New western diet (NWD) TD.96096
  • vitamin D3 (1alpha,25-(OH)2-D3) (VD3)
  • Calcium-enriched
 Intestine

0
C57BL/6J Intestine carcinoma - invasive
  • New western diet (NWD) TD.96096
  • Folic acid-enriched
 Intestine

0
C57BL/6J Intestine carcinoma - invasive
  • New western diet (NWD) TD.96096
 Intestine

0
C57BL/6J Intestine carcinoma - invasive
  • choline-enriched
  • New western diet (NWD) TD.96096
 Intestine

0
C57BL/6J Intestine lesion
  • AIN-76A
 Intestine

0
C57BL/6J Intestine lesion
  • New western diet (NWD) TD.96096
 Intestine

0
C57BL/6J Intestine lesion
  • New western diet (NWD) TD.96096
  • vitamin D3 (1alpha,25-(OH)2-D3) (VD3)
  • Calcium-enriched
 Intestine

0
C57BL/6J Intestine lesion
  • New western diet (NWD) TD.96096
  • Folic acid-enriched
 Intestine

0
C57BL/6J Intestine lesion
  • choline-enriched
  • New western diet (NWD) TD.96096
 Intestine

0
C57BL/6J Intestine lesion
  • methionine-enriched
  • New western diet (NWD) TD.96096
 Intestine

0
C57BL/6J Intestine lesion
  • New western diet (NWD) TD.96096
  • high fiber
 Intestine

0
C57BL/6J Intestine tumor
  • (see notes regarding diet)
 Intestine

observed
C57BL/6J Intestine tumor
  • AIN-76A
 Intestine

0 - 26.67
C57BL/6J Intestine tumor
  • New western diet (NWD) TD.96096
 Intestine

0 - 53.33
C57BL/6J Intestine tumor
  • New western diet (NWD) TD.96096
  • vitamin D3 (1alpha,25-(OH)2-D3) (VD3)
  • Calcium-enriched
 Intestine

5.56 - 15.38
C57BL/6J Intestine tumor
  • New western diet (NWD) TD.96096
  • Folic acid-enriched
 Intestine

7.14 - 44.44
C57BL/6J Intestine tumor
  • choline-enriched
  • New western diet (NWD) TD.96096
 Intestine

13.04 - 33.33
C57BL/6J Intestine tumor
  • methionine-enriched
  • New western diet (NWD) TD.96096
 Intestine

22.22 - 37.5
C57BL/6J Intestine tumor
  • New western diet (NWD) TD.96096
  • high fiber
 Intestine

5.88 - 35.29
C57BL/6J Leukocyte - Monocyte - Macrophage - Kupffer cell sarcoma
  • (see notes regarding diet)
 Liver

observed
C57BL/6J Leukocyte lymphoma - non-Hodgkin
  • (see notes regarding diet)
 Leukocyte

observed - 3.93
C57BL/6J Leukocyte lymphoma - non-Hodgkin
  • AIN-76A
 Leukocyte

observed
C57BL/6J Liver hepatoblastoma
  • (see notes regarding diet)
 Liver

observed
C57BL/6J Liver tumor
  • (see notes regarding diet)
 Liver

observed - 2.81
C57BL/6J Liver tumor
  • AIN-76A
 Liver

observed
C57BL/6J Liver tumor
  • methionine-enriched
  • New western diet (NWD) TD.96096
 Liver

0
C57BL/6J Lung - Alveolus adenoma
  • (see notes regarding diet)
 Lung - Alveolus

observed
C57BL/6J Lung - Alveolus carcinoma
  • (see notes regarding diet)
 Lung - Alveolus

observed
C57BL/6J Lung - Bronchiole adenoma
  • (see notes regarding diet)
 Lung - Bronchiole

observed
C57BL/6J Lung - Bronchiole carcinoma
  • (see notes regarding diet)
 Lung - Bronchiole

observed
C57BL/6J Lung tumor
  • (see notes regarding diet)
 Lung

observed - 4.21
C57BL/6J Lung tumor
  • AIN-76A
 Lung

observed
C57BL/6J Muscle - Smooth leiomyosarcoma
  • (see notes regarding diet)
 (Unspecified organ)

observed
C57BL/6J Stomach adenoma - microadenoma
  • AIN-76A
 Stomach

0
C57BL/6J Stomach adenoma - microadenoma
  • New western diet (NWD) TD.96096
 Stomach

0 - observed
C57BL/6J Stomach adenoma - microadenoma
  • New western diet (NWD) TD.96096
  • vitamin D3 (1alpha,25-(OH)2-D3) (VD3)
  • Calcium-enriched
 Stomach

0
C57BL/6J Stomach adenoma - microadenoma
  • New western diet (NWD) TD.96096
  • Folic acid-enriched
 Salivary gland

0
C57BL/6J Stomach adenoma - microadenoma
  • choline-enriched
  • New western diet (NWD) TD.96096
 Stomach

0
C57BL/6J Stomach adenoma - microadenoma
  • methionine-enriched
  • New western diet (NWD) TD.96096
 Stomach

0
C57BL/6J Stomach adenoma - microadenoma
  • New western diet (NWD) TD.96096
  • high fiber
 Stomach

0
C57BL/6J (Unspecified organ) tumor
  • (see notes regarding diet)
 (Unspecified organ)

observed - 14.47
C57BL/6J (Unspecified organ) tumor
  • AIN-76A
 (Unspecified organ)

observed - 6.67
C57BL/6J (Unspecified organ) tumor
  • New western diet (NWD) TD.96096
  • high fiber
 (Unspecified organ)

0