Carcinogenesis Advance Access published online on June 20, 2008
Carcinogenesis, doi:10.1093/carcin/bgn144
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Upregulation of p21Waf1/Cip1 expression in vivo by butyrate administration can be chemoprotective or chemopromotive depending on the lipid component of the diet1
2 Faculty of Nutrition, Texas A&M University, College Station, TX 77843-2253
3 Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843-2253
4 Center for Environmental and Rural Health, Texas A&M University, College Station, TX 77843-2253
5 Corresponding author and to whom reprint requests should be addressed: Dr. Joanne R. Lupton, 213 Kleberg Center, 2253 TAMU Texas A&M University, College Station, TX 77843-2253 Phone: (979) 845-0850, Fax: (979) 862-1862. Email: Jlupton{at}tamu.edu
The overall goal of this research was to separate out the effects of butyrate from its fiber source and determine in vivo if it upregulates colonic histone acetylation, p21Waf1/Cip1 expression, and apoptosis and if this sequelae of events is protective against aberrant crypt formation (ACF). Eighty SD rats were provided defined diets with either corn oil or fish oil as the lipid source, +/– butyrate-containing capsules targeted for release in the colon, and +/– azoxymethane (AOM) (10 rats/group). Diets were provided for 11 weeks and at termination colonocyte nuclear histone H4 and p21Waf1/Cip1 (p21) expression were determined by immunohistochemistry; apoptosis was measured by the TUNEL assay; and aberrant crypt numbers and multiplicity were enumerated. Luminal butyrate levels were also quantified. AOM injection repressed p21 expression, which was reversed by butyrate supplementation. Although butyrate enhanced p21 expression with both dietary lipid sources, the increase in p21 resulted in an increase in apoptosis and decrease in ACF with fish oil, but had no effect on apoptosis and increased ACF with corn oil. This significant interaction between fat, butyrate (fiber) and p21 expression, with one combination being protective and the other promotive of colon carcinogenesis reinforces the importance of considering diet as a key factor in chemoprevention.
Key Words: n-3 fatty acids • fish oil • butyrate • fiber • colon cancer
1 This work was supported by NIH CA 61750, CA 59034, CA 82907, NIEHS P30-ES-09106 and the National Space Biomedical Research Institute (NASA NCC 9-58).
Received October 5, 2007; revised May 19, 2008; accepted June 3, 2008.
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