title: Effects of dietary fish oil on the depletion of carcinogenic PAH-DNA adduct levels in the liver of B6C3F1 mouse.
abstract: Many carcinogenic polycyclic aromatic hydrocarbons (PAHs) and their metabolites can bind covalently to DNA. Carcinogen-DNA adducts may lead to mutations in critical genes, eventually leading to cancer. In this study we report that fish oil (FO) blocks the formation of DNA adducts by detoxification of PAHs. B6C3F1 male mice were fed a FO or corn oil (CO) diet for 30 days. The animals were then treated with seven carcinogenic PAHs including benzo(a)pyrene (BaP) with one of two doses via a single intraperitoneal injection. Animals were terminated at 1, 3, or 7 d after treatment. The levels of DNA adducts were analyzed by the (32)P-postlabeling assay. Our results showed that the levels of total hepatic DNA adducts were significantly decreased in FO groups compared to CO groups with an exception of low PAH dose at 3 d (P = 0.067). Total adduct levels in the high dose PAH groups were 41.36±6.48 (Mean±SEM) and 78.72±8.03 in 10(9) nucleotides (P = 0.011), respectively, for the FO and CO groups at 7 d. Animals treated with the low dose (2.5 fold lower) PAHs displayed similar trends. Total adduct levels were 12.21±2.33 in the FO group and 24.07±1.99 in the CO group, P = 0.008. BPDE-dG adduct values at 7 d after treatment of high dose PAHs were 32.34±1.94 (CO group) and 21.82±3.37 (FO group) in 10(9) nucleotides with P value being 0.035. Low dose groups showed similar trends for BPDE-dG adduct in the two diet groups. FO significantly enhanced gene expression of Cyp1a1 in both the high and low dose PAH groups. Gstt1 at low dose of PAHs showed high levels in FO compared to CO groups with P values being 0.014. Histological observations indicated that FO played a hepatoprotective role during the early stages. Our results suggest that FO has a potential to be developed as a cancer chemopreventive agent.
authors: Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, Texas, United States of America. gzhou@ibt.tamhsc.edu
authors: Guo-Dong
authors: GD
authors: Zhou
authors: Huiping
authors: H
authors: Zhu
authors: Tracie D
authors: TD
authors: Phillips
authors: Jianbo
authors: J
authors: Wang
authors: Shi-Zhou
authors: SZ
authors: Wang
authors: Fen
authors: F
authors: Wang
authors: Brad A
authors: BA
authors: Amendt
authors: Xanthi I
authors: XI
authors: Couroucli
authors: Kirby C
authors: KC
authors: Donnelly
authors: Bhagavatula
authors: B
authors: Moorthy
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000378:metabolism*; D018736:DNA Adducts / Q000378:metabolism*; D004032:Diet; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D005227:Fatty Acids / Q000032:analysis; D005395:Fish Oils / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D050216:Metabolic Detoxication, Phase I / Q000235:genetics; D050217:Metabolic Detoxication, Phase II / Q000235:genetics; D051379:Mice; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism*
chemical_list: D002273:Carcinogens; D018736:DNA Adducts; D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; D005395:Fish Oils; D011084:Polycyclic Aromatic Hydrocarbons; C095911:polycyclic aromatic hydrocarbons-DNA adduct