Effects of Dietary Fish Oil on the Depletion of Carcinogenic PAH-DNA Adduct Levels in the Liver of B6C3F1 Mouse

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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Comparison of the levels of BPDE-dG adduct in liver of mice between the two diet groups.

<p>FO significantly reduced the levels of BPDE-dG adducts at 3 (low PAH dose only) or 7 day time points. For animal treatment information, please see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026589#pone-0026589-g002" target="_blank">Figure 2</a>. Mean ± SEM, n = 4.</p

Typical representative pattern of ³²P-postlabeled PAH-DNA adducts in mouse liver.

<p>Mice, fed with dietary FO, were treated with high dose of PAH mixture. Animals were terminated at 7 days after treatment.</p

Fatty acids in fish oil and corn oil.

<p>*n-3 = 0.99%, n-6 = 0.41%;</p><p>**n-3 = 1.4%, n-6 = 0.9%;</p><p>***n-3/n-6.</p

Comparison of the levels of total DNA adducts in liver of mice between two diet groups.

<p>Mice were treated with high or low dose of PAH mixtures. Animals were terminated at 1, 3 or 7 days after treatment. Overall, dietary FO decreased the levels of PAH adducts compared to CO groups. Except for low PAH dose at 3 days, the differences of adduct values between two diet groups were significant. Mean ± SEM, n = 4.</p

Mouse body weights.

<p>n = 35.</p

Diet composition.

<p>Diet composition.</p

Effects of dietary fish oil on hepatic gene expression of some metabolic enzymes.

<p>*2∧(−(Ct value − β-actin value − 15));</p><p>**2∧(−(Ct value − β-actin value − 3));</p><p>n = 4.</p