Phenobarbital induces progressive patterns of GC-rich and gene-specific altered DNA methylation in the liver of tumor-prone B6C3F1 mice

Toxicological Sciences : an Official Journal of the Society of Toxicology
Ammie N BachmanJay I Goodman

Abstract

Altered DNA methylation contributes to tumorigenesis by affecting gene expression in a heritable fashion. Phenobarbital (PB) is a nongenotoxic rodent carcinogen which induces global hypomethylation and regions of hypermethylation in mouse liver. Liver tumor-sensitive (B6C3F1) and -resistant (C57BL/6) male mice were administered 0.05% (wt/wt) PB in drinking water for 2 or 4 weeks, and a 2-week recovery was included following each dosing period. DNA was isolated from liver (target) and kidney (nontarget) tissues. The methylation status of GC-rich regions of DNA was assessed via methylation-sensitive restriction digestion, arbitrarily primedpolymerase chain reaction, and capillary electrophoretic separation of products. PB-induced regions of altered methylation (RAMs) which carry forward from an early to a later time point are more likely to be mechanistically relevant as compared to those that do not. Twelve of 69 RAMs (17%) present in B6C3F1 liver at 2 weeks were also seen at 4 weeks, while only 1 of the 123 RAMs (< 1%) present in C57BL/6 liver was seen at 4 weeks. In the B6C3F1 mice, 57 unique (as compared to the C57BL/6) regions of altered hepatic methylation (RAMs), predominantly hypomethylation, were observed at 2 weeks, inc...Continue Reading

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Citations

Sep 27, 2012·Cancer Letters·Igor P Pogribny, Frederick A Beland
Mar 25, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jennifer M Phillips, Jay I Goodman
Feb 24, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jennifer M Phillips, Jay I Goodman
Mar 10, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jennifer M PhillipsJay I Goodman
Jun 2, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jennifer M PhillipsJay I Goodman
Jan 8, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Emily A McClureJay I Goodman
Oct 24, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Harri LempiäinenJonathan G Moggs
Dec 15, 2010·Environmental Health Perspectives·Igor KoturbashIvan Rusyn
Dec 1, 2009·Epigenomics·Igor P Pogribny
Nov 29, 2013·Epigenomics·Alexander LairdRichard R Meehan
Jan 9, 2014·Briefings in Functional Genomics·Tim D WilliamsJ Kevin Chipman
Mar 21, 2008·International Journal of Cancer. Journal International Du Cancer·Christina Leah B KlineRosalyn B Irby
Sep 5, 2013·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·John P ThomsonRichard R Meehan
Mar 31, 2015·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Lidia LuzhnaOlga Kovalchuk
Dec 19, 2006·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jennifer M PhillipsJay I Goodman
May 28, 2010·Toxicology and Industrial Health·Grazyna KostkaBozena Wiadrowska
Aug 7, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Moshe Szyf
Sep 9, 2011·PloS One·Marco ConstanteMark Isalan
Oct 17, 2019·Life Science Alliance·Antonio VitobelloRémi Terranova
Oct 1, 2020·Annual Review of Pharmacology and Toxicology·Miklos Toth

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