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A. Agrawal



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    P2.01 - Poster Session 2 - Cancer Biology (ID 145)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.01-018 - Defective DNA damage response in lungs of asthmatics: A possible link to lung cancer? (ID 952)

      09:30 - 09:30  |  Author(s): A. Agrawal

      • Abstract

      Background
      The new lifestyle adaptations in the developing countries altered the environment and these contribute in the development of various respiratory diseases like asthma, COPD, etc. Though it is well known that COPD may lead to development of lung cancer, the effect of asthma on lung cancer development is not well studied. Lung cancer is a leading cause of mortality worldwide as more than a million people die every year. Few recent meta-analytic studies showed a positive correlation between asthma and lung cancer. But, there are no reports to demonstrate the status of DNA damage in asthma.

      Methods
      8-hydroxydeoxyguanosine, DNA damage marker, was measured in BAL fluids and sera samples of human asthmatics. To see the gene expression related to DNA damage response, we performed the quantitative Real Time PCR array in human normal and asthmatic lungs. Significantly altered genes were validated at mRNA as well as in protein levels by using western blotting and immunohistochemistry.

      Results
      Increased levels of 8-hydroxydeoxyguanosine was observed in BAL fluids and sera of human asthmatics. Human and murine asthmatic lungs show an increase in the expression of 8-hydroxy-2'-deoxyguanosine. In comparison to normal, human asthmatics showed a decrease in the expression of key DNA damage response proteins like gamma-H2AX, Atm, chk2, Mre11 and DNA-pkcs.

      Conclusion
      For the first time, we have shown that there may be defective DNA damage response in asthmatics which might link asthma to lung cancer. As various meta-analysis studies indicate a positive correlation between asthma and lung cancer, it is necessary to delineate the mechanisms underlying this.