title: 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.affiliation: Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Christine Guo
authors.initials: CG
authors.lastname: Lian
authors.affiliation: Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Shuyun
authors.initials: S
authors.lastname: Xu
authors.affiliation: Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Weimin
authors.initials: W
authors.lastname: Guo
authors.affiliation: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas.
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.affiliation: Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Maximilian Y M
authors.initials: MY
authors.lastname: Frank
authors.affiliation: Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Robert
authors.initials: R
authors.lastname: Liu
authors.affiliation: Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Liu
authors.affiliation: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: George F
authors.initials: GF
authors.lastname: Murphy
authors.affiliation: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000818:Animals; D034341:Aristolochic Acids / Q000633:toxicity*; D063646:Carcinogenesis / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D009154:Mutation / Q000187:drug effects; D009369:Neoplasms / Q000139:chemically induced / Q000378:metabolism; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D055647:Rats, Transgenic
chemical_list: D034341:Aristolochic Acids; D002273:Carcinogens; D004268:DNA-Binding Proteins; D011763:Pyrrolizidine Alkaloids; C011865:5-hydroxymethylcytosine; C013672:riddelliine; D044503:5-Methylcytosine; D003596:Cytosine; C000228:aristolochic acid I
keywords: 5-hydroxymethylcytosine; aristolochic acid; carcinogenesis; mutagenesis; riddelliine; ten-eleven translocation