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Publication : Role of polyamines in arginine-dependent colon carcinogenesis in Apc(Min) (/+) mice.

First Author  Yerushalmi HF Year  2006
Journal  Mol Carcinog Volume  45
Issue  10 Pages  764-73
PubMed ID  16705737 Mgi Jnum  J:115819
Mgi Id  MGI:3692234 Doi  10.1002/mc.20246
Citation  Yerushalmi HF, et al. (2006) Role of polyamines in arginine-dependent colon carcinogenesis in Apc(Min) (/+) mice. Mol Carcinog 45(10):764-73
abstractText  We evaluated the role of polyamines in arginine-dependent intestinal tumorigenesis in Apc(Min) (/+) 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-alpha-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 Apc(Min) (/+) mice. Inhibition of polyamine synthesis suppresses the arginine-dependent risk of colon tumorigenesis, resulting in apoptosis induction and decreased tumorigenesis, in this murine model.
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