Modulation of the epigenome in fish carcinogenesis

Leda Mirbahai, Ning Li, Timothy Williams, Ulf Sommer, John P Bignell, Brett P Lyons, Grant D Stentiford, zhiyuan gong, Huiqing Zhan, Mark Viant, James Chipman

Research output: Contribution to journalAbstract

Abstract

The etiology of cancer is complex, with genetic and epigenetic factors contributing to its development. The epigenome is highly susceptible to environmental factors, resulting in increased risk of development of cancer in response to certain environmental signals. However, in contrast to the wealth of information available on environmental factors, epigenomic changes and development of cancer in humans, this area is substantially understudied in aquatic biology. Recently we have demonstrated that chemically induced liver tumours in zebrafish (Danio rerio) have a similar epigenetic signature to human liver tumours. Furthermore, we have investigated the epigenetic abnormalities linked to high incidence of liver tumours in dab (Limanda limanda), a specie commonly used in biomonitoring. It has been reported that the incidence of liver tumours in these fish exceed 20% at some offshore UK locations. Our data revealed a remarkable and consistent global hypomethylation, disruption of the one-carbon pathway and modifications of CpG island methylation and transcriptome in histologically normal liver tissue distal to tumours compared to livers of non-tumour-bearing fish. The mechanism of this disruption is linked to a decrease in choline and elevated S-adenosylhomocysteine, a potent inhibitor of DNA methytransferases. These findings imply a degree of conservation of epigenetic abnormalities important in tumourigenesis among vertebrates. They also offer novel opportunities for monitoring of conditions with potential to affect the epigenome in the environment, with major implications on tumourigenesis, fish survival, biodiversity and environmental risk assessment of chemical contaminants.
Original languageEnglish
Article numberS17
JournalToxicology Letters
Volume229
Issue numberSupplement
DOIs
Publication statusPublished - 10 Sep 2014
Event50th Congress of the European Societies of Toxicology (EUROTOX) - Edinburgh, United Kingdom
Duration: 7 Sep 201410 Sep 2014

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