Skip to main content
SpringerLink
Log in

Uranium induces apoptosis in lung epithelial cells

  • Organ Toxicity and Mechanisms
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Uranium is a naturally occurring radioactive material present everywhere in the environment. It is toxic because of its chemical or radioactive properties. Uranium enters environment mainly from mines and industry and cause threat to human health by accumulating in lungs as a result of inhalation. In our previous study, we have shown the effectiveness of antioxidant system response to the oxidative stress induced by uranyl acetate (UA) in rat lung epithelial (LE) cells. As part of our continuing studies; here, we investigated the mechanism underlying when LE cells are exposed to different concentration of UA. Oxidative stress may lead to apoptotic signaling pathways. LE cells treated with 0.25, 0.5 and 1 mM of UA results in dose and time-dependent increase in activity of both caspases-3 and -8. Increase in the concentration of cytochrome-c oxidase in cytosol was seen in LE cells treated with 1 mM UA as a result of mitochondria membrane permeability. The cytochrome-c leakage may trigger the apoptotic pathway. TUNEL assay performed in LE cells treated with 1 mM of UA showed significant incorporation of dNTPs in the nucleus after 24 h. In the presence of the caspase inhibitors, we observed the significant decrease in the activity of caspases-8 and -3 in 0.5 and 1 mM UA-treated LE cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Bertin G, Averbeck D (2006) Cadmium: cellular effects, modifications of biomolecules, modulation of DNA repair and genotoxic consequences (a review). Biochimie 88:1549–1559

    Article  PubMed  CAS  Google Scholar 

  • Bin W, James FT, Terry SW, Gary SS (2006) In vitro immune toxicity of depleted uranium: effects on murine macrophages, CD4 + T cells, and gene expression profiles. Environ Health Perspect 114(1):85–91

    Google Scholar 

  • Bleise A, Danesi PR, Burkart W (2003) Properties, use and health effects of depleted uranium (DU): a general overview. J Environ Radioact 64:93–112

    Article  PubMed  CAS  Google Scholar 

  • Bradley RH, Caldwell BM (1978) Screening the environment. Am J Orthopsychiatry 48(1):114–130

    Article  PubMed  CAS  Google Scholar 

  • Celine T, Marie C, Sarah M, Angelique S, Laure A, Barbara G (2007) Uranium induces apoptosis and is genotoxic to normal rat kidney (NRK-52E) proximal cells. Toxicol Sci 98(2):479–487

    Article  CAS  Google Scholar 

  • Chobanova N, Genchev G, Yagova A, Georgieva L (2003) Cancer in populations living in regions with radio ecological problems in Bulgaria. J BUON (official journal of the Balkan Union of Oncology 8(2):143–146

    CAS  Google Scholar 

  • Grosche B, Kreuzer M, Kreisheimer M, Schnelzer M, Tschense A (2006) Lung cancer risk among German male uranium miners: a cohort study, 1946–1998. Br J Cancer 95:1280–1287

    Article  PubMed  CAS  Google Scholar 

  • Ivan S (2006) Common mechanisms in nephropathy induced by toxic metals. Nephron Physiol 104:107–114

    Article  CAS  Google Scholar 

  • James KA, Andrew GP (2007) Apoptosis commitment—translating survival signals into decisions on mitochondria. Cell Res 17:976–984

    Article  CAS  Google Scholar 

  • Joachim S, Monika P, Paria Y, Thilo D, Hans-Joachim W (2007) ATM gene mutations in former uranium miners of SDAG Wismut: a pilot study. Oncol Rep 17:477–482

    Google Scholar 

  • John KF, Narayani R, Vilmar V, David ME (2002) Depleted uranium/uranyl chloride induces apoptosis in mouse J774 macrophages. Toxicology 179:105–114

    Article  Google Scholar 

  • Kanno S, Kitajima Y, Kakuta M, Osanai Y, Kurauchi K, Ujibe M, Ishikawa M (2008) Costunolide-induced apoptosis is caused by receptor-mediated pathway and inhibition of telomerase activity in NALM-6 cells. Biol Pharm Bull 5:1024–1028

    Article  Google Scholar 

  • Kendra CL, Geoffrey HG (2007) Regulation of the cellular DNA double-strand break response. Biochem Cell Biol 85:663–674

    Article  CAS  Google Scholar 

  • Klervi L, Solenne B, Dominique B, Margot T, Sylvaine C, Benoıt Q, Dominique L (2007) Lung cancer risk associated to exposure to radon and smoking in a case–control study of French uranium miners. Health Phys 92(4):371–378

    Article  CAS  Google Scholar 

  • Kryscio A, Ulrich Muller WU, Wojcik A, Kotschy N, Grobelny S, Streffer C (2001) A cytogenetic analysis of the long-term effect of uranium mining on peripheral lymphocytes using the micronucleus—centromere assay. Int J Radiat Biol 77(11):1087–1093

    Article  PubMed  CAS  Google Scholar 

  • Levine S, Saltzman A (1994) The balance between lymphatic and systemic absorption determines the outcome of sensitization for anaphylaxis in rats. Int Arch Allergy Immunol 105(1):91–95

    Article  PubMed  CAS  Google Scholar 

  • Marjorie M, Michel MD, Francxois P, Valerie C, Gerard D, Marie D (2006) Genotoxic and inflammatory effects of depleted uranium particles inhaled by rats. Toxicol Sci 89(1):287–295

    Google Scholar 

  • Monica Y, Shania GL, Edgar CR, Diane SM (2003) Uranyl acetate causes DNA single strand breaks in-vitro in the presence of ascorbate (Vitamin C). Chem Res Toxicol 16(4):524–530

    Article  CAS  Google Scholar 

  • Padmavati S, Arora R (1976) Beta-adrenergic blocking agents in cardiology. J Assoc Physicians of India 24(11):725–728

    CAS  Google Scholar 

  • Periyakaruppan A, Kumar F, Sarkar S, Sharma CS, Ramesh GT (2007) Uranium induces oxidative stress in lung epithelial cells. Arch Toxicol 81(6):389–395

    Article  PubMed  CAS  Google Scholar 

  • Prat O, Berenguer F, Malard V, Tavan E, Sage N, Steinmetz G, Quemeneur E (2005) Transcriptomic and proteomic responses of human renal HEK293 cells to uranium toxicity. Proteomics 5:297–306

    Article  PubMed  CAS  Google Scholar 

  • Sandra WS, Douglas TW, AbouEl–Makarim A, Michael MD, John WP Sr (2007) Particulate depleted uranium is cytotoxic and clastogenic to human lung cells. Chem Res Toxicol 20(5):815–820

    Article  CAS  Google Scholar 

  • Seon–Hee O, Sung–Chul L (2006) A rapid and transient ROS generation by cadmium triggers apoptosis via caspase-dependent pathway in HepG2 cells and this is inhibited through N-acetylcysteine-mediated catalase upregulation. Toxicol Appl Pharmacol 212:212–223

    Article  CAS  Google Scholar 

  • Seon–Hee O, Byung-Hoon L, Sung-Chul L (2004) Cadmium induces apoptotic cell death in WI 38 cells via caspase-dependent Bid cleavage and calpain-mediated mitochondrial Bax cleavage by Bcl-2-independent pathway. Biochem Pharmacol 68:1845–1855

    Article  CAS  Google Scholar 

  • Susumu O, Ying X, Motohide T (1998) Effects of uranium ore dust on cultured human lung cells. Environ Toxicol Pharmacol 5(4):267–271

    Article  Google Scholar 

  • The Royal Society Working Group on the Health Hazards of Depleted Uranium Munitions (2002) The health effects of depleted uranium munitions: a summary. J Radiol Prot 22:131–139

    Article  Google Scholar 

  • US Department of Health and Human Services (1999) Toxicological profile for uranium. Agency for Toxic Substances and Disease Registry 462

  • Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160:1–40

    Article  PubMed  CAS  Google Scholar 

  • Veronique M, Odette P, Elisabeth D, Frederic B, Nicole S, Eric Q (2005) Proteomic analysis of the response of human lung cells to uranium. Proteomics 5:4568–4580

    Article  CAS  Google Scholar 

  • Vincent G, Saadia K, Gerard G, Marc P, Herve R (2004) Uranium induces TNF-α secretion and MAPK activation in a rat alveolar macrophage cell line. Toxicol Appl Pharmacol 194:49–59

    Article  CAS  Google Scholar 

  • Virginia CH, Diane SM (2006) Molecular analysis of hprt mutations generated in Chinese hamster ovary EM9 cells by uranyl acetate, by hydrogen peroxide, and spontaneously. Mol Carcinog 45:60–72

    Article  CAS  Google Scholar 

  • World Health Organization (2001) Health effects of depleted uranium. Fifty-fourth World Health Assembly A54/19:Add.1

  • Yang ZH, Fan BX, Lu Y, Cao ZS, Yu S, Fan FY, Zhu MX (2002) Malignant transformation of human bronchial epithelial cell (BEAS-2B) induced by depleted uranium. Ai-Zheng (Chin J Cancer) 21(9):944–948

    Google Scholar 

Download references

Acknowledgments

This work was supported by NASA funding NCC 9-165: NCC-1-02038: NAG 9-1414: NIH 1P20MD001822-1 (GR).

Author information

Authors and Affiliations

  1. Molecular Toxicology Laboratory, Department of Biology, Center for Biotechnology and Biomedical Sciences, Norfolk State University, Norfolk, VA, 23504, USA

    Prabakaran Ravichandran, Chidananda S. Sharma, Vani Ramesh, Joseph C. Hall & Govindarajan T. Ramesh

  2. Environmental Toxicology Program, Department of Chemistry, Texas Southern University, Houston, TX, 77004, USA

    Adaikkappan Periyakaruppan, Shubhashish Sarkar, Bindu Sadanandan, Renard Thomas & Bobby L. Wilson

Authors
  1. Adaikkappan Periyakaruppan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shubhashish Sarkar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Prabakaran Ravichandran
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bindu Sadanandan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chidananda S. Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vani Ramesh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Joseph C. Hall
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Renard Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bobby L. Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Govindarajan T. Ramesh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Govindarajan T. Ramesh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Periyakaruppan, A., Sarkar, S., Ravichandran, P. et al. Uranium induces apoptosis in lung epithelial cells. Arch Toxicol 83, 595–600 (2009). https://doi.org/10.1007/s00204-008-0396-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-008-0396-5

Keywords

Search

Navigation