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Showcasing the 3Rs
Research projects from 50 different groups was presented on the day and there was an even mix from academia and industry, communicating work across all three 'R's. Prizes were awarded for the presenters who most successfully communicated their work to the guests on the day. A judging panel of 15, chaired by Lord Turnberg, assessed the entries and awarded three prizes of £2k, one each for Replacement, Refinement and Reduction. The Replacement Prize was presented by Phil Willis and was won by Kelly BéruBé and Tracy Hughes from Cardiff University's School of Biosciences, for their work to find a possible alternative to animal testing in the field of Inhalation Toxicology. The Refinement Prize was presented by Dr Philip Wright of the ABPI, and was won by Claire Rourke, GlaxoSmithKline, for her work investigating a novel way to give laboratory rodents doses of drugs for testing. The Reduction Prize was presented by Dr David Lynn of the Wellcome Trust and was won by Richard Walmsley, University of Manchester, and Paul Hastwell, GlaxoSmithKline, and Nick Billinton of Gentronix Ltd for their work in improving the identification of cancer causing chemicals using cell cultures. A press release was issued to highlight the event and an abstract booklet (PDF, 1.7 MB) was produced which briefly describes the work that was presented, in the words of the researchers involved. Below are details of the winning posters, including links to download them. Winner of the Replacement PrizeA possible alternative to animal testing in the field of Inhalation Toxicology (PDF, 553KB) Tracy Hughes, Dominique Balharry, Keith Sexton, Timothy Jones and Kelly BéruBé Recent legislation has accentuated the importance of development of alternative toxicology testing methods which avoid the use of animals, particularly for inhalation toxicity. The focus of this study was to develop a sensitive human based cellular model to identify initial signals of damage to lung epithelial composition and native protection systems, inflicted by inhaled particles. The aim was to establish key levels at which these particles cause irreversible damage to lung tissue using specific target cells, (human-derived normal human bronchial epithelial cells [NHBE]). To observe changes in cellular responses, primary cells sampled from humans, were grown to form a 3-dimensional (3D) cell culture. The 3D cultures formed tight junctions between cells, cells with active cilia, and others producing and secreting mucus. These characteristics closely resemble those found in the native human respiratory epithelial tissue, and should accurately mimic the human responses to tissue damage. An integrated analysis of the development of the cultures was used to establish key physical and corresponding biochemical changes. This was achieved using light and electron microscopy and various chemical assays. The ability of the epithelial cells to form strong inter-cellular junctions was confirmed by measuring the resistance to an electrical current. Cellular activity (viability) was assessed using a colour changing metabolic dye. Protein secretion and mucin gene expression was also examined, to more fully assess the representative nature of the tissue model. The human airway epithelium is just one component of a very complex human physiological response to inhaled particles, however, it being one of the first targets, a better understanding of its response will help to shed light on the corresponding effects. The NHBE cell model provides a human-based representative alternative to animal testing in the field of inhalation toxicology. Winner of the Refinement PrizeInvestigation of a novel refined oral dosing method (PDF, 235KB) Claire Rourke and Darrel Pemberton When using animals to research and test new drugs it is common to administer these drugs orally to laboratory rodents, typically using the gavage technique. Essentially, this method consists of (1) manually restraining the animal, (2) inserting a small diameter tube (which can be rigid or flexible) into the oesophagus and (3) delivering the drug directly into the stomach by means of a syringe. Although highly effective and reliable, this method may occasionally cause oesophageal injury and will cause some restraint-induced stress, particularly with repeated use. The aim of this study was to assess a novel oral dosing administration that could potentially reduce the stress and injury associated with this standard gavage technique. Over six days, male Lister hooded rats were trained to drink from a syringe containing either a 5-10% sucrose solution or 1mg/ml donepezil (Aricept", an approved medicine for treatment of Alzheimer's Disease) suspended in 5-10% sucrose solution. On each day, the time taken for each animal to drink their respective treatments was recorded. There were no significant differences in the time taken to drink the whole solution between the donepezil and sucrose treated animals, demonstrating that the donepezil suspension was no less palatable than sucrose alone. After just a few days training, there were significant reductions in the average time taken for animals to drink their respective treatments. Moreover, on day six, animals' consumption of their respective treatments via the syringe was far quicker than the oral gavage method. In summary, the novel oral dosing method clearly offers a number of advantages over the oral gavage method in reducing restraint-induced stress and potential oesophageal injury. Winner of the Reduction PrizeImproved early identification of cancer causing chemicals in cell cultures could reduce animal testing (PDF, 403KB) Richard Walmsley, Gentronix, Paul Hastwell, GlaxoSmithKline, and Nick Billinton, Gentronix Cancer can arise as a consequence of the chromosome damage caused by UV in sunlight, radioactivity, and chemicals known as 'genotoxins'. For this reason, all chemicals have to be tested for genotoxicity. However, the current 'test tube' genotoxicity test methods using mammalian cells are seriously inaccurate: they mis-classify over 50% of safe chemicals as potential carcinogens. As a result additional animal studies have to be carried out to determine the likely cancer risk typically using over 200 for a new pharmaceutical. A simple new test ('GreenScreen HC') has been developed by the University of Manchester spinout company Gentronix Ltd to tackle the accuracy problem. Exploiting recent advances in our understanding of the human genome and cutting edge genomic technologies, an engineered human cell line has been produced that glows green when exposed to genotoxins. Testing of over 150 compounds by Gentronix and GSK has shown that the new test is highly predictive of the regulatory animal tests, with over 95% accuracy in the identification of genotoxic carcinogens. More importantly however, it very effectively discriminates between those chemicals that are truly genotoxic and the safe chemicals that regulatory test tube methods have misclassified as hazardous. In a collection of 28 such misclassified chemicals, 26 (over 90%) gave the correct negative result with GreenScreen. Use of this new test on these chemicals could have prevented 52 animal studies. The inaccuracy of existing cancer hazard assessment methods can lead to the loss of potentially valuable new pharmaceuticals, industrial chemicals and household products. The accuracy of the new test could save money and many animal lives imminent REACH legislation will require over 30,000 compounds to be tested. Related Documents
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