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Prevention and Epidemiology

Dietary Fish Oil Alters T Lymphocyte Cell Populations and Exacerbates Disease in a Mouse Model of Inflammatory Colitis

Hillary L. Woodworth, Sarah J. McCaskey, David M. Duriancik, Jonathan F. Clinthorne, Ingeborg M. Langohr, Elizabeth M. Gardner and Jenifer I. Fenton
Hillary L. Woodworth
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Sarah J. McCaskey
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David M. Duriancik
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Jonathan F. Clinthorne
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Ingeborg M. Langohr
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Elizabeth M. Gardner
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Jenifer I. Fenton
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DOI: 10.1158/0008-5472.CAN-10-1396 Published October 2010
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Abstract

Inflammatory bowel diseases (IBD) increase the risk of developing colorectal cancer. Dietary components that reduce inflammation are associated with lower cancer risk. The long-chain omega-3 fatty acid docosahexaenoic acid (DHA) is present in fish oil and has potent anti-inflammatory properties. The objective of this study is to determine whether dietary fish oil enriched with DHA (DFO) could reduce experimentally induced colitis and colon cancer risk in a mouse model. When SMAD3−/− mice are exposed to Helicobacter hepaticus, mild colitis is observed 4 weeks postinfection. Mice were fed isocaloric diets modified to include corn oil, safflower oil, or DFO (doses ranging from 0.75% to 6.00%) as the fatty acid source for 8 weeks. Mice were gavaged with H. hepaticus; DFO feeding was continued; and mice were sacrificed 4 weeks after infection. The colon and cecum were collected for histopathology. Spleens and mesenteric lymph nodes were collected and analyzed for T-cell populations using flow cytometry. Contrary to expectations, DFO induced severe colitis and adenocarcinoma formation. DFO consumption was associated with decreased CD8+ cell frequency and diminished CD69 expression on CD4+ and CD8+ T-cell populations. Mice consuming DFO also exhibited higher FoxP3+ CD25+ CD4+ T regulatory cell frequency, FoxP3 expression, and altered L-selectin expression during infection. We concluded that DFO-fed mice may be less equipped to mount a successful response to H. hepaticus infection, increasing colon cancer risk. These results support the need to establish a tolerable upper limit for DHA intake particularly in the context of chronic inflammatory conditions such as IBD. Cancer Res; 70(20); 7960–9. ©2010 AACR.

  • Received April 19, 2010.
  • Revision received June 14, 2010.
  • Accepted July 20, 2010.
  • ©2010 American Association for Cancer Research.
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Cancer Research: 70 (20)
October 2010
Volume 70, Issue 20
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Dietary Fish Oil Alters T Lymphocyte Cell Populations and Exacerbates Disease in a Mouse Model of Inflammatory Colitis
Hillary L. Woodworth, Sarah J. McCaskey, David M. Duriancik, Jonathan F. Clinthorne, Ingeborg M. Langohr, Elizabeth M. Gardner and Jenifer I. Fenton
Cancer Res October 15 2010 (70) (20) 7960-7969; DOI: 10.1158/0008-5472.CAN-10-1396

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Dietary Fish Oil Alters T Lymphocyte Cell Populations and Exacerbates Disease in a Mouse Model of Inflammatory Colitis
Hillary L. Woodworth, Sarah J. McCaskey, David M. Duriancik, Jonathan F. Clinthorne, Ingeborg M. Langohr, Elizabeth M. Gardner and Jenifer I. Fenton
Cancer Res October 15 2010 (70) (20) 7960-7969; DOI: 10.1158/0008-5472.CAN-10-1396
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