Toxicological Research

  • 제26권4호
  • /
  • Pages.261-266
  • /
  • 2010
  • /
  • 1976-8257(pISSN)
  • /
  • 2234-2753(eISSN)
한국독성학회 (Korean Society of Toxicology & Korea Environmental Mutagen Society)
권호 표지
DOI QR코드

DOI QR Code

Inhalation Toxicity of Particulate Matters Doped with Arsenic Induced Genotoxicity and Altered Akt Signaling Pathway in Lungs of Mice

  • Park, Jin-Hong (Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University) ;
  • Kwon, Jung-Taek (Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University) ;
  • Minai-Teherani, Arassh (Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University) ;
  • Hwang, Soon-Kyung (Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University) ;
  • Chang, Seung-Hee (Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University) ;
  • Lim, Hwang-Tae (Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University) ;
  • Cho, Hyun-Seon (Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University) ;
  • Cho, Myung-Haing (Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University)
  • 투고 : 2010.06.07
  • 심사 : 2010.08.25
  • 발행 : 2010.12.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

In the workplace, the arsenic is used in the semiconductor production and the manufacturing of pigments, glass, pesticides and fungicides. Therefore, workers may be exposed to airborne arsenic during its use in manufacturing. The purpose of this study was to evaluate the potential toxicity of particulate matters (PMs) doped with arsenic (PMs-Arsenic) using a rodent model and to compare the genotoxicity in various concentrations and to examine the role of PMs-Arsenic in the induction of signaling pathway in the lung. Mice were exposed to PMs $124.4{\pm}24.5\;{\mu}g/m^3$ (low concentration), $220.2{\pm}34.5\;{\mu}g/m^3$ (middle concentration), $426.4{\pm}40.3\;{\mu}g/m^3$ (high concentration) doped with arsenic $1.4\;{\mu}g/m^3$ (Low concentration), $2.5\;{\mu}g/m^3$ (middle concentration), $5.7\;{\mu}g/m^3$ (high concentration) for 4 wks (6 h/d, 5 d/wk), respectively in the whole-body inhalation exposure chambers. To determine the level of genotoxicity, Chromosomal aberration (CA) assay in splenic lymphocytes and Supravital micronucleus (SMN) assay were performed. Then, signal pathway in the lung was analyzed. In the genotoxicity experiments, the increases of aberrant cells were concentration-dependent. Also, PMs-arsenic caused peripheral blood micronucleus frequency at high concentration. The inhalation of PMs-Arsenic increased an expression of phosphorylated Akt (p-Akt: protein kinase B) and phpsphorylated mammalian target of rapamycin (p-mTOR) at high concentration group. Taken together, inhaled PMs-Arsenic caused genotoxicity and altered Akt signaling pathway in the lung. Therefore, the inhalation of PMs-Arsenic needs for a careful risk assessment in the workplace.

키워드

참고문헌

  1. Beck, B.D., Slayton, T.M., Farr, C.H., Sved, D.W., Crecelius, E.A. and Holson, J.F. (2002). Systemic uptake of inhaled arsenic in rabbits. Hum. Exp. Toxicol., 21, 205-215. https://doi.org/10.1191/0960327102ht237oa
  2. de Kok, T.M., Hogervorst, J.G., Briede, J.J., van Herwijnen, M.H., Maas, L.M., Moonen, E.J., Driece, H.A. and Kleinjans, J.C. (2005). Genotoxicity and physicochemical characteristics of traffic-related ambient particulate matter. Environ. Mol. Mutagen., 46, 71-80. https://doi.org/10.1002/em.20133
  3. Dockery, D.W. and Pope, C.A., 3rd. (1994). Acute respiratory effects of particulate air pollution. Annu. Rev. Public. Health, 15, 107-132. https://doi.org/10.1146/annurev.pu.15.050194.000543
  4. Donaldson, K. and MacNee, W. (2001). Potential mechanisms of adverse pulmonary and cardiovascular effects of particulate air pollution (PM10). Int. J. Hyg. Environ. Health, 203, 411-415. https://doi.org/10.1078/1438-4639-00059
  5. Dong, Z. (2002). The molecular mechanisms of arsenic-induced cell transformation and apoptosis. Environmental Health Perspectives, 110, 757. https://doi.org/10.1289/ehp.02110757
  6. Enterline, P.E., Day, R. and Marsh, G.M. (1995). Cancers related to exposure to arsenic at a copper smelter. Occup. Environ. Med., 52, 28-32. https://doi.org/10.1136/oem.52.1.28
  7. Hathaway, G.J., Proctor, N.H., Hughes, J.P. and Fischman, M.L. (1991) Chemical Hazards of the workplace. 2nd ed. Van Nostrand Reinhold Co, New York.
  8. Hayashi, H., Kanisawa, M., Yamanaka, K., Ito, T., Udaka, N., Ohji, H., Okudela, K., Okada, S. and Kitamura, H. (1998). Dimethylarsinic acid, a main metabolite of inorganic arsenics, has tumorigenicity and progression effects in the pulmonary tumors of A/J mice. Cancer. Lett., 125, 83-88. https://doi.org/10.1016/S0304-3835(97)00484-9
  9. Holson, J.F., Stump, D.G., Ulrich, C.E. and Farr, C.H. (1999). Absence of prenatal developmental toxicity from inhaled arsenic trioxide in rats. Toxicol. Sci., 51, 87-97. https://doi.org/10.1093/toxsci/51.1.87
  10. Hopenhayn-Rich, C., Biggs, M.L. and Smith, A.H. (1998). Lung and kidney cancer mortality associated with arsenic in drinking water in Cordoba, Argentina. Int. J. Epidemiol. 27, 561-569. https://doi.org/10.1093/ije/27.4.561
  11. Kim, M.Y., Kim, Y.C. and Cho, M.H. (2002). Combined treatment with 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone and dibutyl phthalate enhances ozone-induced genotoxicity in B6C3F1 mice. Mutagenesis., 17, 331-336. https://doi.org/10.1093/mutage/17.4.331
  12. Noda, Y., Suzuki, T., Kohara, A., Hasegawa, A., Yotsuyanagi, T., Hayashi, M., Sofuni, T., Yamanaka, K. and Okada, S. (2002). In vivo genotoxicity evaluation of dimethylarsinic acid in Muta- Mouse. Mutat Res., 513, 205-212. https://doi.org/10.1016/S1383-5718(01)00313-8
  13. Oberdorster, G., Oberdorster, E. and Oberdorster, J. (2005). Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ. Health Perspect., 113, 823-839. https://doi.org/10.1289/ehp.7339
  14. Papadimitrakopoulou, V. and Adjei, A.A. (2006). The Akt/mTOR and mitogen-activated protein kinase pathways in lung cancer therapy. J. Thorac. Oncol., 1, 749-751. https://doi.org/10.1097/01243894-200609000-00031
  15. Park, J.H., Han, K.T., Eu, K.J., Kim, J.S., Chung, K.H., Park, B., Yang, G.S., Lee, K.H. and Cho, M.H. (2005). Diffusion flamederived fine particulate matters doped with iron caused genotoxicity in B6C3F1 mice. Toxicol. Ind. Health, 21, 57-65. https://doi.org/10.1191/0748233705th215oa
  16. Partridge, M.A., Huang, S.X., Hernandez-Rosa, E., Davidson, M.M. and Hei, T.K. (2007). Arsenic induced mitochondrial DNA damage and altered mitochondrial oxidative function: implications for genotoxic mechanisms in mammalian cells. Cancer Res., 67, 5239-5247. https://doi.org/10.1158/0008-5472.CAN-07-0074
  17. Petrick, J.S., Ayala-Fierro, F., Cullen, W.R., Carter, D.E. and Vasken Aposhian, H. (2000). Monomethylarsonous acid (MMA(III)) is more toxic than arsenite in Chang human hepatocytes. Toxicol. Appl. Pharmacol., 163, 203-207. https://doi.org/10.1006/taap.1999.8872
  18. Pope, C.A., 3rd. (2000). Epidemiology of fine particulate air pollution and human health: biologic mechanisms and who’s at risk? Environ. Health Perspect., 108, 713-723. https://doi.org/10.2307/3454408
  19. Pope, C.A., 3rd, Burnett, R.T., Thun, M.J., Calle, E.E., Krewski, D., Ito, K. and Thurston, G.D. (2002). Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. JAMA, 28, 1132-1141.
  20. Roubicek, D.A., Gutierrez-Castillo, M.E., Sordo, M., Cebrian-Garcia, M.E. and Ostrosky-Wegman, P. (2007). Micronuclei induced by airborne particulate matter from Mexico City. Mutat Res., 631, 9-15. https://doi.org/10.1016/j.mrgentox.2007.04.001
  21. Rudel, R., Slayton, T.M. and Beck, B.D. (1996). Implications of arsenic genotoxicity for dose response of carcinogenic effects. Regul. Toxicol. Pharmacol., 23, 87-105. https://doi.org/10.1006/rtph.1996.0031
  22. Schins, R.P., Lightbody, J.H., Borm, P.J., Shi, T., Donaldson, K. and Stone, V. (2004). Inflammatory effects of coarse and fine particulate matter in relation to chemical and biological constituents. Toxicol. Appl. Pharmacol., 195, 1-11. https://doi.org/10.1016/j.taap.2003.10.002
  23. Song, G., Ouyang, G. and Bao, S. (2005). The activation of Akt/PKB signaling pathway and cell survival. J. Cell. Mol. Med., 9, 59-71. https://doi.org/10.1111/j.1582-4934.2005.tb00337.x
  24. Tang, J.M., He, Q.Y., Guo, R.X. and Chang, X.J. (2006). Phosphorylated Akt overexpression and loss of PTEN expression in non-small cell lung cancer confers poor prognosis. Lung Cancer., 51, 181-191. https://doi.org/10.1016/j.lungcan.2005.10.003
  25. Tchounwou, P.B., Wilson, B. and Ishaque, A. (1999). Important considerations in the development of public health advisories for arsenic and arsenic-containing compounds in drinking water. Rev. Environ. Health, 14, 211-229. https://doi.org/10.1515/REVEH.1999.14.4.211
  26. Vega, L., Styblo, M., Patterson, R., Cullen, W., Wang, C. and Germolec, D. (2001). Differential effects of trivalent and pentavalent arsenicals on cell proliferation and cytokine secretion in normal human epidermal keratinocytes. Toxicol. Appl. Pharmacol., 172, 225-232. https://doi.org/10.1006/taap.2001.9152
  27. Yang, L., Dan, H.C., Sun, M., Liu, Q., Sun, X.M., Feldman, R.I., Hamilton, A.D., Polokoff, M., Nicosia, S.V., Herlyn, M. and others (2004). Akt/protein kinase B signaling inhibitor-2, a selective small molecule inhibitor of Akt signaling with antitumor activity in cancer cells overexpressing Akt. Cancer Res., 64, 4394-4399. https://doi.org/10.1158/0008-5472.CAN-04-0343