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Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
Impact of dietary fatty acids on 7,12-dimethylbenz[a]anthracene-induced mammary DNA adducts
1Department of Nutrition, Pennsylvania State University, University Park 16802, USA.
Abstract:
These studies examined the impact of dietary corn oil and its major constituent fatty acids on the occurrence of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary DNA adducts. In study 1, rats were fed diets containing 5, 10 or 20% corn oil for 2 weeks prior to DMBA treatment (25 mg/kg). Mammary DNA adducts increased significantly (P < 0.05) as the quantity of dietary corn oil increased. Liver glutathione S-transferase (GST) activities increased while UDP-glucuronosyltransferase (UGT) activities decreased as the quantity of dietary corn oil increased. Increased adducts resulting from greater corn oil consumption were positively correlated with GST and negatively correlated with UGT activities. In study 2, rats were fed diets containing 5 or 20% corn oil, or 5% corn oil supplemented with 1.67% palmitic, 3.81% oleic or 8.78% linoleic acid (quantities in 15% corn oil) for 2 weeks prior to DMBA treatment (50 mg/kg). Total mammary DNA adducts were 75, 136 and 156% greater in rats fed the 20% corn oil, oleic acid-supplemented and linoleic acid-supplemented diets, respectively, than in those fed the 5% corn oil diet. Palmitic acid supplementation did not affect the occurrence of adducts. Adducts in study 2 did not correlate with GST or UGT activities. These studies demonstrate that enhanced DMBA bioactivation caused by increased corn oil consumption can be at least partially explained by increased intake of oleic and linoleic acids.
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