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Suppression of Polycyclic Aromatic Hydrocarbon (PAH)‐Mediated Pulmonary Carcinogenesis in Mice by Omega‐3‐Fatty acids
Author(s) -
Moorthy Bhagavatula,
Jiang Weiwu,
Wang Lihua,
Maturu Paramahamsa,
Zhou Guodong
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.694.5
Subject(s) - carcinogen , chemistry , benzo(a)pyrene , carcinogenesis , eicosapentaenoic acid , polycyclic aromatic hydrocarbon , pyrene , docosahexaenoic acid , dna adduct , cytochrome p450 , biochemistry , adduct , fatty acid , pharmacology , medicine , enzyme , polyunsaturated fatty acid , environmental chemistry , biology , organic chemistry , gene
3‐Methylcholanthrene (MC) and benzo[a]pyrene (BP) are potent polycyclic aromatic hydrocarbons (PAHs) carcinogens. PAHs are present in cigarette smoke, diesel exhausts, and charcoal broiled meats, etc. Cytochrome P450 (CYP) 1A/1B1 enzymes play key roles in the activation of PAHs to carcinogenic metabolites, which initiate carcinogenesis by binding covalently to DNA, and the adducts, if not repaired, could lead to tumorigenesis. In this study we tested the hypothesis that pre‐treatment of mice with omega‐3‐fatty acids, i.e. [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) will lead to attenuation of PAH‐mediated pulmonary DNA adduct formation and pulmonary tumorigenesis. Twelve week old male and female A/J mice received EPA (60 mg/kg) and DHA (40 mg/kg) from day 1 to day 24. Control mice were treated with vehicle corn oil. On day 3, mice were treated with BP (40 μmol/kg) or 3‐methylcholanthrene (MC, 40 μmol/kg) by i.p. In the short‐term experiment (DNA adduct studies), 3–5 mice from each group were terminated at day 10 (7 days after BP or MC treatment). EPA/DHA significantly suppressed formation of BP‐DNA and MC‐DNA adducts in lung and liver of both male and female mice. In the long‐term experiment (tumor studies), 8 mice for each group continued to receive EPA/DHA twice per week till end of experiment (16 weeks). Pulmonary tumor incidence and multiplicity was significantly suppressed in mice given EPA+DHA, compared to those given the PAHs, BP or MC alone. PAH treatment led to enhancement of expression of epigenetic genes such as DNMT and EZH2 and repression of RUNX3 in lung. Mice given a combination of PAHs and EPA;/DHA attenuated DNMT and EZH2, but augmented RUNX3. These results suggest that EPA/DHA contribute to the suppression of PAH‐mediated mechanisms in part by modulating epigenetic genes. These studies also suggest that the omega 3‐fatty acids could be developed as novel candidates for the prevention of PAH‐mediated lung cancers in humans. Support or Funding Information R01ES 009132 and R01HL129794 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .