1. Oncogenic ras alters sensitivity of mouse colonocytes to butyrate and fatty acid mediated growth arrest and apoptosis
- Author
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Turner, Nancy D., Zhang, Jianhu, Davidson, Laurie A., Lupton, Joanne R., and Chapkin, Robert S.
- Subjects
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CARCINOGENS , *CHEMOPREVENTION , *APOPTOSIS , *DNA metabolism , *DOCOSAHEXAENOIC acid , *TRIGLYCERIDES , *UNSATURATED fatty acids , *COLON (Anatomy) , *ONCOGENES , *ANIMAL experimentation , *CELL division , *LINOLEIC acid , *DOSE-effect relationship in pharmacology , *OMEGA-3 fatty acids , *RESEARCH funding , *BUTYRIC acid , *MICE - Abstract
Docosahexaenoic acid (DHA) and butyrate favorably modulate colonocyte proliferation and apoptosis. In order to elucidate how oncogenic Ras modulates responses to these chemopreventive nutrients, we incubated isogenic non-transformed and Ras malignant transformed mouse colon cells with butyrate and DHA or linoleic acid (LA). Combining DHA with 1 mM butyrate decreased proliferation relative to LA or no PUFA treatment in both cell lines. At a higher butyrate dose (5 mM), caspase 3 activity was elevated to a greater extent in Ras transformed cells. Only non-transformed cells were sensitive to the apoptogenic effects of DHA, indicating that Ras transformation alters sensitivity to dietary chemopreventive agents. [Copyright &y& Elsevier]
- Published
- 2002
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