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Comparison of DNA damage in human lymphocytes from healthy individuals and asthma, COPD and lung cancer patients treated in vitro / ex vivo with the bulk nano forms of aspirin and ibuprofen

Mojgan Najafzadeh1*, Aftab Ali1, Badie Jacobe2, Muhammad Isreb1, Rajendran Gopalan1 and Lijun Shang1
  • 1 University of Bradford, Medical Sciences, United Kingdom
  • 2 Bradford NHS trus, Bradford Royal Infirmary, United Kingdom

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit COX enzyme activity, a significant mechanism of action of NSAIDs. Inflammation is associated with increasing cancer incidence. Recent pre-clinical and clinical studies have shown that NSAID treatment could cause an anti-tumour effect in cancers. Such studies are lengthy and expensive. The present study, however, examined DNA damage in the Comet and micronucleus assays in peripheral blood lymphocytes of patients with respiratory diseases and healthy individuals using the nanoparticle (NP) and bulk versions of the NSAIDs, aspirin and ibuprofen. Lymphocytes are suitable surrogate cells for cancers and other disease states. DNA damage decreased in lymphocytes from healthy individuals, asthma, COPD and lung cancer patient groups after treatment with aspirin nano-suspension (ASP N) and ibuprofen nano-suspension (IBU N) compared to their bulk version (micro-suspension) in both assays. However, when ASP N was compared to untreated lymphocytes in all groups in the Comet assay, DNA damage significantly decreased in all groups, except the asthma group. When IBU N was compared to untreated lymphocytes, in healthy individuals and the lung cancer group, DNA damage decreased, but increased in asthma and COPD groups. Similarly, micronuclei (MNi) increased after ASP N and IBU N in the healthy individual and lung cancer groups, and decreased in asthma and COPD groups. Also shows that whilst there are basic similarities with different genetic endpoints in terms of nano and bulk forms, but highlights some differences between the disease states examined. Furthermore, lymphocyte responses after IBU N and ibuprofen bulk were investigated by patch-clamp experiments demonstrating that IBU N inhibited ion channel activity by 20%. This molecular epidemiology approach mirrors pre-clinical and clinical findings, and provides new information using nanoparticles.

Acknowledgements

The authors would like to thank Bilal Khorsheed from Lena nanoceutics for supplying the nano-suspensions. Also we thank Yuling Ma and Clive Ellory for their help in the preliminary work on electrophysiology.

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Keywords: : DNA damage, lung cancer, COPD, Asthma, Nanoparticles, bulk forms aspirin, Ibuprofen

Conference: ICAW 2015 - 11th International Comet Assay Workshop, Antwerpen, Belgium, 1 Sep - 4 Sep, 2015.

Presentation Type: Poster Presentation

Topic: Genotoxicity testing of chemicals and nanomaterials

Citation: Najafzadeh M, Ali A, Jacobe B, Isreb M, Gopalan R and Shang L (2015). Comparison of DNA damage in human lymphocytes from healthy individuals and asthma, COPD and lung cancer patients treated in vitro / ex vivo with the bulk nano forms of aspirin and ibuprofen. Front. Genet. Conference Abstract: ICAW 2015 - 11th International Comet Assay Workshop. doi: 10.3389/conf.fgene.2015.01.00059

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Received: 12 May 2015; Published Online: 23 Jun 2015.

* Correspondence: Dr. Mojgan Najafzadeh, University of Bradford, Medical Sciences, Bradford, BD7 1DP, United Kingdom, m.najafzadeh1@bradford.ac.uk