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Cardiovascular Toxicology

, Volume 19, Issue 2, pp 178–190 | Cite as

Effects of Ambient Atmospheric PM2.5, 1-Nitropyrene and 9-Nitroanthracene on DNA Damage and Oxidative Stress in Hearts of Rats

  • Lifang Zhao
  • Li Zhang
  • Minghui Chen
  • Chuan Dong
  • Ruijin LiEmail author
  • Zongwei CaiEmail author
Article
  • 135 Downloads

Abstract

Exposure to fine particulate matter (PM2.5) increased the risks of cardiovascular diseases. PM2.5-bound 1-nitropyrene (1-NP) and 9-nitroanthracene (9-NA) are released from the incomplete combustion of fossil fuels and derived from polycyclic aromatic hydrocarbons (PAHs). The toxicities of 1-NP and 9-NA are mainly reflected in their carcinogenicity and mutagenicity. However, studies of PM2.5-bound 1-NP and 9-NA on the cardiac genotoxicity are limited so far. In this study, histopathology, DNA damage, DNA repair-related gene expression, and oxidative stress were investigated in the hearts of male Wistar rats exposed to PM2.5 [1.5 mg/kg body weight (b.w.)] or three different dosages of 1-NP (1.0 × 10− 5, 4.0 × 10− 5, and 1.6 × 10− 4 mg/kg b.w.) or 9-NA (1.3 × 10− 5, 4.0 × 10− 5, and 1.2 × 10− 4 mg/kg b.w.). The results revealed that (1) PM2.5, higher dosages of 1-NP (4.0 × 10− 5 and 1.6 × 10− 4 mg/kg b.w.) and 9-NA (4.0 × 10− 5 and 1.2 × 10− 4 mg/kg b.w.) caused obvious pathological responses and DNA damage (DNA strand breaks, 8-OHdG formation and DNA–protein cross-link), accompanied by increasing OGG1 and GADD153 expression while inhibiting MTH1 and XRCC1 expression in rat hearts. Also, they elevated the hemeoxygenase-1 (HO-1), glutathione S-transferase (GST), and malondialdehyde (MDA) levels and decreased superoxide dismutase (SOD) activity compared with the control. (2) The lowest dosages 1-NP or 9-NA could not cause DNA damage and oxidative stress. (3) At the approximately equivalent dose level, PM2.5-induced DNA damage effects were more obvious than 1-NP or 9-NA along with positive correlation. Taken together, heart DNA damage caused by PM2.5, 1-NP and 9-NA may be mediated partially through influencing the DNA repair capacity and causing oxidative stress, and such negative effects might be related to the genotoxicity PM2.5, 1-NP, and 9-NA.

Keywords

Fine particulate matter 1-Nitropyrene 9-Nitroanthracene DNA damage Oxidative stress Rat heart 

Notes

Acknowledgements

This research was supported by the National Natural Science Foundation of China (No. 91543202) and the Nature Science Foundation of Shanxi Province in China (No. 2014011036-2).

References

  1. 1.
    IARC. (2016). Outdoor air pollution. In Monographs on the evaluation of carcinogenic risks to humans (Vol. 109). Lyon: IARC.Google Scholar
  2. 2.
    Dominici, F., Peng, R. D., Bell, M. L., Pham, L., McDermot, A., Zeger, S. L., et al. (2006). Fine particulate air pollution and hospital admission for cardiovascular and respiratory diseases. JAMA, 295(10), 1127–1134.Google Scholar
  3. 3.
    Xu, Q., Wang, S., Guo, Y., Wang, C., Huang, F., Li, X., et al. (2017). Acute exposure to fine particulate matter and cardiovascular hospital emergency room visits in Beijing, China. Environmental Pollution, 220(Pt A), 317–327.Google Scholar
  4. 4.
    Thurston, G. D., Burnett, R. T., Turner, M. C., Shi, Y., Krewski, D., Lall, R., et al. (2016). Ischemic heart disease mortality and long-term exposure to source-related components of U.S. fine particle air pollution. Environmental Health Perspectives, 124(6), 785–794.Google Scholar
  5. 5.
    Fu, P. P., & Herreno-Saenz, D. (1999). Nitro-polycyclic aromatic hydrocarbons: A class of genotoxic environmental pollutants. Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis and Ecotoxicology Reviews, 17, 1–43.Google Scholar
  6. 6.
    Yang, X., Igarashi, K., Tang, N., Lin, J. M., Wang, W., Kameda, T., et al. (2010). Indirect- and direct-acting mutagenicity of diesel, coal and wood burning-derived particulates and contribution of polycyclic aromatic hydrocarbons and nitropolycyclic aromatic hydrocarbons. Mutation Research, 695, 29–34.Google Scholar
  7. 7.
    IARC. (2010). Some non-heterocyclic polycyclic aromatic hydrocarbons and some related exposures. In Monographs on the evaluation of carcinogenic risks to humans (Vol. 92). Lyon: IARC.Google Scholar
  8. 8.
    Wang, W., Jariyasopit, N., Schrlau, J., Jia, Y., Tao, S., Yu, T. W., et al. (2011). Concentration and photochemistry of PAHs, NPAHs, and OPAHs and toxicity of PM2.5 during the Beijing Olympic Games. Environmental Science and Technology, 45, 6887–6895.Google Scholar
  9. 9.
    Hayakawa, K. (2016). Environmental behaviors and toxicities of polycyclic aromatic hydrocarbons and nitropolycyclic aromatic hydrocarbons. Chemical and Pharmaceutical Bulletin (Tokyo), 64, 83–94.Google Scholar
  10. 10.
    Jiang, P., Yang, L., Chen, X., Gao, Y., Li, Y., Zhang, J., et al. (2018). Impact of dust storms on NPAHs and OPAHs in PM2.5 in Jinan, China, in spring 2016: Concentrations, health risks, and sources. Aerosol and Air Quality Research, 18, 471–484.Google Scholar
  11. 11.
    Lin, Y., Ma, Y., Qiu, X., Li, R., Fang, Y., & Wang, J., et al. (2015). Sources, transformation, and health implications of PAHs and their nitrated, hydroxylated, and oxygenated derivatives in PM2.5 in Beijing. Journal of Geophysical Research Atmospheres, 120(14), 7219–7228.Google Scholar
  12. 12.
    IARC. (1989). Diesel and gasoline engine exhausts and some nitroarenes. In Monographs on the evaluation of carcinogenic risks to humans (Vol. 46). Lyon: IARC.Google Scholar
  13. 13.
    Andersson, H., Piras, E., Demma, J., Hellman, B., & Brittebo, E. (2009). Low levels of the air pollutant 1-nitropyrene induce DNA damage, increased levels of reactive oxygen species and endoplasmic reticulum stress in human endothelial cells. Toxicology, 262(1), 57–64.Google Scholar
  14. 14.
    Wilson, S. J., Miller, M. R., & Newby, D. E. (2018). Effects of diesel exhaust on cardiovascular function and oxidative stress. Antioxidants and Redox Signaling, 28(9), 819–836.Google Scholar
  15. 15.
    Miller-Schulze, J. P., Paulsen, M., Kameda, T., Toriba, A., Tang, N., Tamura, K., et al. (2013). Evaluation of urinary metabolites of 1-nitropyrene as biomarkers for exposure to diesel exhaust in taxi drivers of Shenyang, China. Journal of Exposure Science and Environmental Epidemiology, 23(2), 170–175.Google Scholar
  16. 16.
    Zhang, Y., Li, R., Fang, J., Wang, C., & Cai, Z. (2018). Simultaneous determination of eighteen nitro-polyaromatic hydrocarbons in PM2.5 by atmospheric pressure gas chromatography–tandem mass spectrometry. Chemosphere, 198, 303–310.Google Scholar
  17. 17.
    Fu, P. P., Heflich, R. H., Von Tungeln, L. S., Yang, D. T., Fifer, E. K., & Beland, F. A. (1986). Effect of the nitro group conformation on the rat liver microsomal metabolism and bacterial mutagenicity of 2- and 9-nitroanthracene. Carcinogenesis, 7(11), 1819–1827.Google Scholar
  18. 18.
    Feng, S., Gao, D., Liao, F., Zhou, F., & Wang, X. (2016). The health effects of ambient PM2.5 and potential mechanisms. Ecotoxicology and Environmental Safety, 128, 67–74.Google Scholar
  19. 19.
    Yang, X., Feng, L., Zhang, Y., Hu, H., Shi, Y., Liang, S., et al. (2018). Cytotoxicity induced by fine particulate matter (PM2.5) via mitochondria-mediated apoptosis pathway in human cardiomyocytes. Ecotoxicology and Environmental Safety, 161, 198–207.Google Scholar
  20. 20.
    Li, R., Kou, X., Geng, H., Xie, J., Tian, J., Cai, Z., et al. (2015). Mitochondrial damage: An important mechanism of ambient PM2.5 exposure-induced acute heart injury in rats. Journal of Hazardous Materials, 287, 392–401.Google Scholar
  21. 21.
    Liu, D., Lin, T., Syed, L. T., Cheng, Z., Xu, Y., Li, K., Zhang, G., et al (2017). Concentration, source identification, and exposure risk assessment of PM2.5-bound parent PAHs and nitro-PAHs in atmosphere from typical Chinese cities. Scientific Reports, 7(1), 10398.Google Scholar
  22. 22.
    Andersson, J. T., & Achten, C. (2015). Time to say goodbye to the 16 EPA PAHs? Toward an up-to-date use of PACs for environmental purposes. Polycyclic Aromatic Compounds, 35(2–4), 330–354.Google Scholar
  23. 23.
    Mayati, A., Le Ferrec, E., Holme, J. A., Fardel, O., Lagadic-Gossmann, D., & Ovrevik, J. (2014). Calcium signaling and β2-adrenergic receptors regulate 1-nitropyrene induced CXCL8 responses in BEAS-2B cells. Toxicology In Vitro, 28(6), 1153–1157.Google Scholar
  24. 24.
    Li, R., Zhao, L., Zhang, L., Chen, M., Dong, C., & Cai, Z. (2017). DNA damage and repair, oxidative stress and metabolism biomarker responses in lungs of rats exposed to ambient atmospheric 1-nitropyrene. Environmental Toxicology and Pharmacology, 54, 14–20.Google Scholar
  25. 25.
    Shang, Y., Zhou, Q., Wang, T., Jiang, Y., Zhong, Y., Qian, G., et al. (2017). Airborne nitro-PAHs induce Nrf2/ARE defense system against oxidative stress and promote inflammatory process by activating PI3K/Akt pathway in A549 cells. Toxicology In Vitro, 44, 66–73.Google Scholar
  26. 26.
    Øvrevik, J., Holme, J. A., Låg, M., Schwarze, P. E., & Refsnes, M. (2013). Differential chemokine induction by 1-nitropyrene and 1-aminopyrene in bronchial epithelial cells: Importance of the TACE/TGF-α/EGFR-pathway. Environmental Toxicology and Pharmacology, 35(2), 235–239.Google Scholar
  27. 27.
    Podechard, N., Tekpli, X., Catheline, D., Holme, J. A., Rioux, V., Legrand, P., et al. (2011). Mechanisms involved in lipid accumulation and apoptosis induced by 1-nitropyrene in Hepa1c1c7 cells. Toxicology Letters, 206(3), 289–299.Google Scholar
  28. 28.
    Li, R., Zhao, L., Zhang, L., Chen, M., Shi, J., Dong, C., et al. (2017). Effects of ambient PM2.5 and 9-nitroanthracene on DNA damage and repair, oxidative stress and metabolic enzymes in lungs of rats. Toxicology Research, 6(5), 654–663.Google Scholar
  29. 29.
    Barzilai, A., & Yamamoto, K. (2004). DNA damage responses to oxidative stress. DNA Repair, 3(8–9), 1109–1115.Google Scholar
  30. 30.
    Bhat, M. A., & Gandhi, G. (2018). Elevated oxidative DNA damage in patients with coronary artery disease and its association with oxidative stress biomarkers. Acta cardiologica.  https://doi.org/10.1080/00015385.2018.1475093.Google Scholar
  31. 31.
    Karahalil, B., Kesimci, E., Emerce, E., Gumus, T., & Kanbak, O. (2011). The impact of OGG1, MTH1 and MnSOD gene polymorphisms on 8-hydroxy-2′-deoxyguanosine and cellular superoxide dismutase activity in myocardial ischemia-reperfusion. Molecular Biology Reports, 38(4), 2427–2435.Google Scholar
  32. 32.
    Papeo, G. (2016). MutT Homolog 1 (MTH1): The silencing of a target. Journal of Medicinal Chemistry, 59(6), 2343–2345.Google Scholar
  33. 33.
    Risom, L., Møller, P., & Loft, S. (2005). Oxidative stress-induced DNA damage by particulate air pollution. Mutation Research, 592(1–2), 119–137.Google Scholar
  34. 34.
    Cao, L. X., Geng, H., Yao, C. T., Zhao, L., Duan, P. L., et al. (2014). Investigation of chemical compositions of atmospheric fine particles during a wintertime haze episode in Taiyuan City. China Environmental Science, 34(4), 837–843.Google Scholar
  35. 35.
    Xie, J., Fan, R., & Meng, Z. (2007). Protein oxidation and DNA–protein crosslink induced by sulfur dioxide in lungs livers, and hearts from mice. Inhalation Toxicology, 19, 759–765.Google Scholar
  36. 36.
    Shah, A. S., Langrish, J. P., Nair, H., McAllister, D. A., Hunter, A. L., Donaldson, K., et al. (2013). Global association of air pollution and heart failure: A systematic review and meta-analysis. Lancet, 382(9897), 1039–1048.Google Scholar
  37. 37.
    Mustafic, H., Jabre, P., Caussin, C., Murad, M. H., Escolano, S., Tafflet, M., et al. (2012). Main air pollutants and myocardial infarction: A systematic review and meta-analysis. JAMA, 307(7), 713–721.Google Scholar
  38. 38.
    Liang, R., Zhang, B., Zhao, X., Ruan, Y., Lian, H., & Fan, Z. (2014). Effect of exposure to PM2.5 on blood pressure: A systematic review and meta-analysis. Journal of Hypertension, 32(11), 2130–2140.Google Scholar
  39. 39.
    Xie, X., Wang, Y., Yang, Y., Xu, J., Zhang, Y., Tang, W., et al. (2018). Long-term exposure to fine particulate matter and tachycardia and heart rate: Results from 10 million reproductive-age adults in China. Environmental Pollution, 242(Pt B), 1371–1378.Google Scholar
  40. 40.
    Lee, M. S., Eum, K. D., Fang, S. C., Rodrigues, E. G., Modest, G. A., & Christiani, D. C. (2014). Oxidative stress and systemic inflammation as modifiers of cardiac autonomic responses to particulate air pollution. International Journal of Cardiology, 176(1), 166–170.Google Scholar
  41. 41.
    Chu, M., Sun, C., Chen, W., Jin, G., Gong, J., Zhu, M., et al. (2015). Personal exposure to PM2.5, genetic variants and DNA damage: A multi-center population-based study in Chinese. Toxicology Letters, 235(3), 172–178.Google Scholar
  42. 42.
    Wu, J., Shi, Y., Asweto, C. O., Feng, L., Yang, X., Zhang, Y., et al. (2017). Fine particle matters induce DNA damage and G2/M cell cycle arrest in human bronchial epithelial BEAS-2B cells. Environmental Science and Pollution Research, 24(32), 25071–25081.Google Scholar
  43. 43.
    Meng, Z., & Zhang, Q. (2007). Damage effects of dust storm PM2.5 on DNA in alveolar macrophages and lung cells of rats. Food and Chemical Toxicology, 45(8), 1368–1374.Google Scholar
  44. 44.
    Cakmakoglu, B., Aydin, M., & Cincin, Z. B. (2011). Effect of oxidative stress on DNA repairing genes, INTECH Open Access Publisher.  https://doi.org/10.5772/21054.Google Scholar
  45. 45.
    Nemmar, A., Beegam, S., Yuvaraju, P., Yasin, J., Tariq, S., Attoub, S., et al. (2016). Ultrasmall superparamagnetic iron oxide nanoparticles acutely promote thrombosis and cardiac oxidative stress and DNA damage in mice. Particle and Fibre Toxicology, 13(1), 22.Google Scholar
  46. 46.
    Zhang, P., Yi, L. H., Meng, G. Y., Zhang, H. Y., Sun, H. H., & Cui, L. Q. (2017). Apelin-13 attenuates cisplatin-induced cardiotoxicity through inhibition of ROS-mediated DNA damage and regulation of MAPKs and AKT pathways. Free Radical Research, 51(5), 449–459.Google Scholar
  47. 47.
    Bai, Y., Jiang, L. P., Liu, X. F., Wang, D., Yang, G., Geng, C. Y., et al. (2015). The role of oxidative stress in citreoviridin-induced DNA damage in human liver-derived HepG2 cells. Environmental Toxicology, 30(5), 530–537.Google Scholar
  48. 48.
    Tokarz, P., Kaarniranta, K., & Blasiak, J. (2016). Inhibition of DNA methyltransferase or histone deacetylase protects retinal pigment epithelial cells from DNA damage induced by oxidative stress by the stimulation of antioxidant enzymes. European Journal of Pharmacology, 776, 167–175.Google Scholar
  49. 49.
    Sharma, R., Yang, Y., Sharma, A., Awasthi, S., & Awasthi, Y. C. (2004). Antioxidant role of glutathione S-transferases: Protection against oxidant toxicity and regulation of stress-mediated apoptosis. Antioxidants and Redox Signaling, 6(2), 289–300.Google Scholar
  50. 50.
    Takahashi, T., Morita, K., Akagi, R., & Sassa, S. (2004). Heme oxygenase-1: A novel therapeutic target in oxidative tissue injuries. Current Medicinal Chemistry, 11(12), 1545–1561.Google Scholar
  51. 51.
    Hwang, E. S., & Kim, G. H. (2007). Biomarkers for oxidative stress status of DNA, lipids, and proteins in vitro and in vivo cancer research. Toxicology, 229(1–2), 1–10.Google Scholar
  52. 52.
    Arnold Groehler, I. V., Kren, S., Li, Q., Robledo-Villafane, M., Schmidt, J., Garry, M., et al. (2018). Oxidative cross-linking of proteins to DNA following ischemia-reperfusion injury. Free Radical Biology and Medicine, 120, 89–101.Google Scholar
  53. 53.
    Sagai, M., Saito, H., Ichinose, T., Kodama, M., & Mori, Y. (1993). Biological effects of diesel exhaust particles. I. In vitro production of superoxide and in vivo toxicity in mouse. Free Radical Biology and Medicine, 14(1), 37–47.Google Scholar
  54. 54.
    Kim, Y. D., Ko, Y. J., Kawamoto, T., & Kim, H. (2005). The effects of 1-nitropyrene on oxidative DNA damage and expression of DNA repair enzymes. Journal of Occupational Health, 47, 261–266.Google Scholar
  55. 55.
    Luethy, J. D., & Holbrook, N. J. (1992). Activation of the GADD153 promoter by genotoxic agents: A rapid and specific response to DNA damage. Cancer Research, 52(1), 5–10.Google Scholar
  56. 56.
    Jeong, J. K., Stevens, J. L., Lau, S. S., & Monks, T. J. (1996). Quinone thioether-mediated DNA damage, growth arrest, and gadd153 expression in renal proximal tubular epithelial cells. Molecular Pharmacology, 50(3), 592–598.Google Scholar
  57. 57.
    Nallanthighal, S., Chan, C., Murray, T. M., Mosier, A. P., Cady, N. C., & Reliene, R. (2017). Differential effects of silver nanoparticles on DNA damage and DNA repair gene expression in OGG1-deficient and wild type mice. Nanotoxicology, 11(8), 1–16.Google Scholar
  58. 58.
    Hanssen-Bauer, A., Solvang-Garten, K., Akbari, M., & Otterlei, M. (2012). X-ray repair cross complementing protein 1 in base excision repair. International Journal of Molecular Sciences, 13(12), 17210–17229.Google Scholar
  59. 59.
    Oh, S. M., Kim, H. R., Yong, J. P., Lee, S. Y., & Chung, K. H. (2011). Organic extracts of urban air pollution particulate matter (PM2.5)-induced genotoxicity and oxidative stress in human lung bronchial epithelial cells (BEAS-2B cells). Mutation Research, 723(2), 142–151.Google Scholar

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Authors and Affiliations

  1. 1.Institute of Environmental ScienceShanxi UniversityTaiyuanPeople’s Republic of China
  2. 2.State Key Laboratory of Environmental and Biological Analysis, Department of ChemistryHong Kong Baptist UniversityJiulongChina

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