Effect of dibromoacetic acid on DNA methylation, glycogen accumulation, and peroxisome proliferation in mouse and rat liver

Toxicological Sciences : an Official Journal of the Society of Toxicology
L TaoM A Pereira

Abstract

Dibromoacetic acid (DBA) is a drinking water disinfection by-product. Its analogs, dichloroacetic acid (DCA) and trichloroacetic acid (TCA), are liver carcinogens in rodents. We evaluated the ability of DBA to cause DNA hypomethylation, glycogen accumulation, and peroxisome proliferation that are activities previously reported for the two other haloacetic acids. Female B6C3F1 mice and male Fischer 344 rats were administered 0, 1,000, and 2,000 mg/l DBA in drinking water. The animals were euthanized after 2, 4, 7, and 28 days of exposure. Dibromoacetic acid caused a dose-dependent and time-dependent decrease of 20%-46% in the 5-methylcytosine content of DNA. Hypomethylation of the c-myc gene was observed in mice after 7 days of DBA exposure. Methylation of 24 CpG sites in the insulin-like growth factor 2 (IGF-II) gene was reduced from 80.2% +/- 9.2% to 18.8% +/- 12.9% by 2,000 mg/l DBA for 28 days. mRNA expression of the c-myc and IGF-II genes in mouse liver was increased by DBA. A dose-dependent increase in the mRNA expression of the c-myc gene was also observed in rats. In both mice and rats, DBA caused dose-dependent accumulation of glycogen and an increase of peroxisomal lauroyl-CoA oxidase activity. Hence, DBA, like DCA and...Continue Reading

Citations

Oct 21, 2010·Journal of Immunotoxicology·Matthew J SmithKimber L White
Sep 15, 2010·Environmental and Molecular Mutagenesis·Michael J PlewaElizabeth D Wagner
Dec 9, 2014·Epigenetics : Official Journal of the DNA Methylation Society·Lucas A SalasNúria Malats
Jun 9, 2015·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Jaromir MichałowiczMarta Kwiatkowska
Aug 2, 2015·Current Environmental Health Reports·Cristina M VillanuevaPatrick Levallois
May 28, 2010·Toxicology and Industrial Health·Grazyna KostkaBozena Wiadrowska
Jul 15, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Lianhui TaoMichael A Pereira

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