title: Hydroquinone induces DNA hypomethylation-independent overexpression of retroelements in human leukemia and hematopoietic stem cells.
abstract: Hydroquinone (HQ) is an important benzene-derived metabolite associated with acute myelogenous leukemia risk. Although altered DNA methylation has been reported in both benzene-exposed human subjects and HQ-exposed cultured cells, the inventory of benzene metabolite effects on the epigenome is only starting to be established. In this study, we used a monocytic leukemia cell line (THP-1) and hematopoietic stem cells (HSCs) from cord blood to investigate the effects of HQ treatment on the expression of the three most important families of retrotransposons in the human genome: LINE-1, Alu and Endogenous retroviruses (HERVs), that are normally subjected to tight epigenetic silencing. We found a clear tendency towards increased retrotransposon expression in response to HQ exposure, more pronounced in the case of LINE-1 and HERV. Such a partial loss of silencing, however, was generally not associated with HQ-induced DNA hypomethylation. On the other hand, retroelement derepression was also observed in the same cells in response to the hypomethylating agent decitabine. These observations suggest the existence of different types of epigenetic switches operating at human retroelements, and point to retroelement activation in response to benzene-derived metabolites as a novel factor deserving attention in benzene carcinogenesis studies.
authors.affiliation: Department of Life Sciences, University of Parma, Parma, Italy.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Conti
authors.affiliation: EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, University of Milano, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Rota
authors.affiliation: Cell Factory, Unit of Cell Therapy and Cryobiology, Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Ragni
authors.affiliation: EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, University of Milano, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Favero
authors.affiliation: EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, University of Milano, Milan, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Motta
authors.affiliation: Cell Factory, Unit of Cell Therapy and Cryobiology, Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Lazzari
authors.affiliation: EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, University of Milano, Milan, Italy; Epidemiology Unit, Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bollati
authors.affiliation: EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, University of Milano, Milan, Italy; Epidemiology Unit, Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Fustinoni
authors.affiliation: Department of Life Sciences, University of Parma, Parma, Italy. Electronic address: giorgio.dieci@unipr.it.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Dieci
mesh_terms: D002460:Cell Line; D004247:DNA / Q000235:genetics*; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006873:Hydroquinones / Q000008:administration & dosage*; D007938:Leukemia / Q000235:genetics*; D018626:Retroelements / Q000187:drug effects / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D006873:Hydroquinones; D018626:Retroelements; D004247:DNA; C031927:hydroquinone
keywords: Benzene; Environmental epigenetics; Hematopoietic stem cells; Hydroquinone; Leukemia; Retrotransposon