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 32P-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 109 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 109 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.

Preservation of Metabolic Flexibility in Skeletal Muscle by a Combined Use of n-3 PUFA and Rosiglitazone in Dietary Obese Mice

“…This gene is inducible by both TZDs [73], and PUFA [74], acts both as epoxygenase and hydroxylase, while producing PUFA-derived lipid mediators, with EPA-derived lipid mediators exerting presumably anti-inflammatory effects [53].…”

Increased susceptibility to hyperoxic lung injury and alveolar simplification in newborn rats by prenatal administration of benzo[a]pyrene

“…The radioactively labeled adducts were separated by multidirectional anion-exchange thin-layer chromatography (TLC) on polyethyleneimine-cellulose sheets and chromatographed overnight (~15 hr) in the first direction (D1) with 2.3 M sodium phosphate, pH 5.75, to purify bulky adducts. The bulky labeled DNA adducts retained in the D1 chromatogram were contact-transferred to fresh thin-layer sheets and adducts were separated two-dimensionally with 3.82 M lithium formate, 6.75 M urea, pH 3.35, and 0.72 M sodium phosphate, 0.40 M Tris, 7.65 M urea, pH 8.20, for the first and second dimensions, respectively (Zhou et al, 2011). Radioactive spots were located by imaging using an Instant Imager from Packard Instrument Co. (800 Research Parkway, Meriden, CT 06450) and by screen-enhanced autoradiography on Kodak XAR-5 X-ray film at -80°C for 22 h. The adducts were expressed as 1 in 10 9 relative adduct labeling (RAL) values, as reported previously (Reddy and Randerath, 1986; Zhou et al, 2011).…”

Protective Effects of Fish Oil Omega-3 Supplement on Liver-related Biochemical Factors Changes Induced by Thioacetamide in Male Rats

“…Kim et al (2013) showed that diet containing Omega-3 can attenuate Hepatic damage caused by ischemia and tissue Reperfusion via reduction of NF-Kb activity 24 .At the same time, Popescu et al (2013) indicated that Omega-3 fatty acid along with diet containing natural calorie and diet with natural lipid has protective effects on nonalcoholic fatty liver disease 25 .Other studies have shown that fish oil diet prevents hepatocyte cancer in B6C3F1 mice 26 .Similarly, Omega-3-rich fish oil improves liver damage caused by LPS through the inhibition of TLR4 signaling pathway and NOD 27 .…”