Genetic alterations and cancer formation in a European flatfish at sites of different contamination burdens

Lerebours, Adelaide; Stentiford, Grant; Bignell, John P.; Lyons, Brett P.; Derocles, Stephane A. P.; Rotchell, Jeanette

Abstract

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 tumor prevalence across sites are poorly understood. This study aims to define 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, pretumor, and tumor pathologies in the livers of 165 fish from six sites in the North Sea and English Channel. The highest concentrations of metals (especially cadmium) and organic chemicals correlated with the presence of tumor pathology and with defined genetic profiles of the Rb gene, from these sites. Different Rb genetic profiles were found in liver tissue near each tumor 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 pretumor disease. This study highlights an association between Rb and specific contaminants (especially cadmium) in the molecular etiology of dab liver tumorigenesis.

Citation

Lerebours, A., Stentiford, G., Bignell, J. P., Lyons, B. P., Derocles, S. A. P., & Rotchell, J. (2014). Genetic alterations and cancer formation in a European flatfish at sites of different contamination burdens. Environmental Science and Technology, 48(17), 10448-10455. https://doi.org/10.1021/es502591p

• Acceptance Date: Aug 7, 2014
• Online Publication Date: Aug 21, 2014
• Publication Date: Sep 2, 2014
• Deposit Date: Apr 29, 2016
• Publicly Available Date: Apr 29, 2016
• Journal: Environmental science and technology
• Print ISSN: 0013-936X
• Electronic ISSN: 1520-5851
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 48
• Issue: 17
• Pages: 10448-10455
• DOI: https://doi.org/10.1021/es502591p
• Keywords: Fish, Liver cancer, Retinoblastoma gene, Genetic changes, Contaminants
• Public URL: https://hull-repository.worktribe.com/output/437459
• Publisher URL: http://pubs.acs.org/doi/abs/10.1021/es502591p
• Additional Information: This document is the Accepted Manuscript version of a Published Work that appeared in final form in Environmental science and technology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/es502591p
• Contract Date: Apr 29, 2016