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

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.

• Authors: Christine Guo Lian, Shuyun Xu, Weimin Guo, Jian Yan, Maximilian Y M Frank, Robert Liu, Cynthia Liu, Ying Chen, George F Murphy, Tao Chen
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 54 Issue 11 Pg. 1503-7 (Nov 2015) ISSN: 1098-2744 [Electronic] United States
• PMID: 25154389 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

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

Topics

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