|Fang, Xiefan -|
|Thornton, Cammi -|
|Willett, Kristine -|
Submitted to: Environmental Toxicology and Pharmacology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 9, 2013
Publication Date: February 28, 2013
Citation: Fang, X., Thornton, C., Scheffler, B.E., Willett, K.L. 2013. Benzo[a]pyrene decreases global and gene specific DNA methylation during zebrafish development. Environmental Toxicology and Pharmacology. p. 40-50. Interpretive Summary: Regulation of gene expression comes from many factors. One of increasing importance to the scientific community is the methylation of DNA. Typically genes that have their DNA heavily methylated have lower gene expression compared to genes with unmethylated DNA. Many factors can impact the level of DNA methylation. In this study the chemical compound benzo[a]pyrene (BaP) was examined for its impact on developing embryos of zebrafish (a model system) in relation to methylation of specific genes. Zebrafish is an ideal model system due to its small size and wealth of scientific data in relation to its genome. The study shows that BaP does have an impact on the overall methylation of zebrafish, but it could not be pinpointed to impact some known genes associated with tumor formation in zebrafish which is important as BaP is characterized as a cacogenic agent.
Technical Abstract: DNA methylation is important for gene regulation and is vulnerable to early-life exposure to environmental contaminants. We found that direct waterborne benzo[a]pyrene (BaP) exposure at 24 'g/L from 2.5 to 96 hours post fertilization (hpf) to zebrafish embryos significantly decreased global cytosine methylation by 44.8% and promoter methylation in vasa by 17%. Consequently, vasa expression was significantly increased by 33%. In contrast, BaP exposure at environmentally relevant concentrations did not change CpG island methylation or gene expression in cancer genes such as ras-association domain family member 1 (rassf1), telomerase reverse transcriptase (tert), c-jun, and c-myca. Similarly, BaP did not change gene expression of DNA methyltransferase 1 (dnmt1) and glycine N-methyltransferase (gnmt). While total DNMT activity was not affected, GNMT enzyme activity was moderately increased. In summary, BaP is an epigenetic modifier for global and gene specific DNA methylation status in zebrafish larvae.