Decrease of 5-hydroxymethylcytosine in rat liver with subchronic exposure to genotoxic carcinogens riddelliine and aristolochic acid

Mol Carcinog. 2015 Nov;54(11):1503-7. doi: 10.1002/mc.22201. Epub 2014 Aug 23.

Abstract

The level of 5-hydroxymethylcytosine (5-hmC) converted by ten-eleven translocation (TET) family is decreased in cancers. However, whether 5-hmC level is perturbed in early stages of carcinogenesis caused by genotoxic carcinogens is not defined. 5-hmC levels and TET2 expression were measured in liver of rats treated with genotoxic carcinogens, riddelliine, or aristolochic acid. Levels of 5-hmC and TET2 expression decreased in the liver of the carcinogens-treated rats. Loss of 5-hmC correlates well with documented induction of genetic mutations by the carcinogens, suggesting that TET2-mediated 5-hydroxymethylation plays an epigenetic role in early state of carcinogenesis.

Keywords: 5-hydroxymethylcytosine; aristolochic acid; carcinogenesis; mutagenesis; riddelliine; ten-eleven translocation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Methylcytosine / analogs & derivatives
  • Animals
  • Aristolochic Acids / toxicity*
  • Carcinogenesis / drug effects
  • Carcinogens / toxicity*
  • Cytosine / analogs & derivatives*
  • Cytosine / metabolism
  • DNA-Binding Proteins / metabolism
  • Epigenesis, Genetic / drug effects
  • Liver / metabolism*
  • Mutation / drug effects
  • Neoplasms / chemically induced
  • Neoplasms / metabolism
  • Pyrrolizidine Alkaloids / toxicity*
  • Rats
  • Rats, Inbred F344
  • Rats, Transgenic

Substances

  • Aristolochic Acids
  • Carcinogens
  • DNA-Binding Proteins
  • Pyrrolizidine Alkaloids
  • 5-hydroxymethylcytosine
  • riddelliine
  • 5-Methylcytosine
  • Cytosine
  • aristolochic acid I