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Inhibition of mammary tumor promotion by dietary D,L-2-difluoromethylornithine in combination with omega-3 and omega-6 fatty acids

Conference · · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)
OSTI ID:6058197
;  [1]
  1. Univ. of Georgia, Athens (United States)
The authors laboratory has shown an inhibitor effect on mammary tumor promotion by a 20% corn oil diet when D,L-2-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC), was fed to female rats with 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors. Analyses of mammary adenocarcinomas from these rats showed that DFMO not only inhibited ODC but also eicosanoid synthesis. Inhibition of tumor promotion, ODC activity and eicosanoid synthesis was additive when dietary combinations of DFMO and menhaden oil were fed. However, when 0.5% DFMO was fed along with 20% dietary fat, signs of toxicity were seen. The overall objective of this study was to establish the minimal and non-toxic dose of DFMO which can give an additive or synergistic antipromoter effect when fed along with dietary n-3 and/or n-6 fatty acids to female Sprague-Dawley rats with DMBA-induced mammary tumors. Four dietary levels of DFMO (0, 0.125, 0.250, and 0.500%) were fed in diets containing 20% fat as either corn, black currant seed or menhaden oil. Dose response effects on tumorigenicity as well as toxicity were noted. Long chain n-3 fatty acids gave greater inhibition of tumorigenesis than shorter chain fatty acids when combined with DFMO. DFMO (0.25%) inhibited tumorigenesis without toxic effects on weight gain, whereas, 0.125% DFMO did not alter tumorigenesis. Supporting biochemical data are presented.
OSTI ID:
6058197
Report Number(s):
CONF-9104107--
Conference Information:
Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (United States) Journal Volume: 4:3
Country of Publication:
United States
Language:
English

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