Role of polyamines in arginine-dependent colon carcinogenesis in Apc(Min) (/+) mice
| Autor: | David E. Stringer, Jose Guillen, Natalia A. Ignatenko, Karen A. Blohm-Mangone, Jose L. Padilla-Torres, Hagit F. Yerushalmi, Claire M. Payne, Eugene W. Gerner, Hana Holubec, David G. Besselsen |
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| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
Arginine Apoptosis Biology medicine.disease_cause chemistry.chemical_compound Basal (phylogenetics) Mice medicine Polyamines Animals Molecular Biology Min mice Polyamine synthesis Animal Feed Colon carcinogenesis Mice Inbred C57BL Cell Transformation Neoplastic chemistry Biochemistry Intestinal Absorption Colonic Neoplasms Cancer research Carcinogens Polyamine Carcinogenesis |
| Zdroj: | Molecular carcinogenesis. 45(10) |
| ISSN: | 0899-1987 |
| Popis: | We evaluated the role of polyamines in arginine-dependent intestinal tumorigenesis in ApcMin/+ mice. Arginine is a substrate for ornithine synthesis and thus can influence polyamine production. Supplementing the diet with arginine increased intestinal and colonic polyamine levels and colonic carcinogenesis. Inhibiting polyamine synthesis with D,L-α-diflouromethylornithine (DFMO) decreased small intestinal and colonic polyamine pools. In mice provided basal diet, but not when supplemented with arginine, DFMO decreased small intestinal tumor number and burden, and increased intestinal apoptosis. In mice provided supplemental arginine in the diet, DFMO induced late apoptosis and decreased tumorigenesis in the colon. DFMO slightly reduced tumor incidence, number, and size while significantly decreasing tumor burden and grade. These changes in colon tumorigenesis did not occur in mice not provided supplemental arginine. Our study indicates that polyamines play unique roles in intestinal and colonic carcinogenesis in ApcMin/+ mice. Inhibition of polyamine synthesis suppresses the arginine-dependent risk of colon tumorigenesis, resulting in apoptosis induction and decreased tumorigenesis, in this murine model. © 2006 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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