An experimental investigation of the effects of radon and its progeny on cultured human cells

contaminated environments, illustrating the importance of considering the potential for wild populations to adapt to their local environment, and its implications for environmental management. Furthermore, we investigated the effects of hypoxia, a common stressor in aquatic systems, on the toxicity of model chemicals to fish. Copper toxicity to zebrafish embryos was strongly affected by hypoxia in a stage-dependent manner. During early embryogenesis, hypoxia strongly suppressed the toxicological effects of copper in a process mediated by the activation of the HIF1 signalling pathway, while after hatching hypoxia increased copper toxicity. Together, our data demonstrate the conservation of molecular pathways of response to environmental chemicals and illustrates the importance of considering the differential susceptibility of wild populations, as well as interactions between multiple stressors, for determining the risk of adverse health outcomes to occur. 4. Molecular epidemiological approach to understanding the development of liver tumours in fish populations Jeanette Rotchell1, Brett Lyons2, Grant Stentiford2, John Bignell2, Adelaide Lerebours3 and Stephane Derocles1 1University of Hull, UK; 2CEFAS, Weymouth, UK; 3University of Portsmouth, UK Fish diseases are an indicator for marine ecosystem health since they provide a biological end-point of historical exposure to stressors. Liver cancer has been used to monitor the effects of exposure to anthropogenic pollution in flatfish for many years. The prevalence of liver cancer can exceed 20%. Despite the high prevalence and the opportunity of using flatfish to study environmentally-induced cancer, the genetic and environmental factors driving tumour prevalence across sites are poorly understood. Using an ‘eco-epidemiological’ approach, we sought to understand the link between genetic deterioration, liver disease progression, and anthropogenic contaminant exposures in the flatfish dab (Limanda limanda). We assessed genetic changes in a conserved cancer gene, Retinoblastoma (Rb) in association with histological diagnosis of normal, pretumour and tumour pathologies in the livers of 165 fish from four sites in the North Sea and English Channel. The highest concentrations of metals (especially cadmium) and organic chemicals correlated with presence of tumour pathology and, with defined genetic profiles of the Rb gene, from these sites. Different Rb genetic profiles were found for each tumour phenotype, giving insight into the mechanistic molecular-level cause of the liver pathologies. Different Rb profiles were also found at sampling sites of differing contaminant burdens. Additionally, profiles indicated that histological ‘normal’ fish from Dogger sampling locations possessed Rb profiles associated with pre-tumour disease, suggesting that such fish are on a pathogenic trajectory towards a liver tumour at these locations. This study highlights the involvement of Rb and specific contaminants (especially cadmium) in the molecular aetiology of dab liver tumourigenesis. 5. Nuclear receptors in the Pacific Oyster, Crassostrea gigas, reveal clear sequence homology to vertebrate species but do not directly promote the use of molluscs as surrogates for vertebrate risk assessment. Tim P. Bean1, Susanne Vogeler1,2, Brett P. Lyons2 and Tamara Galloway2 1Centre for Environment, Fisheries and Aquaculture Science, Cefas Weymouth Laboratory, Barrack Road, Weymouth, UK; 2School of Biosciences, College of Life and Environmental Science, University of Exeter, Stocker