Hydroquinone induces DNA hypomethylation-independent overexpression of retroelements in human leukemia and hematopoietic stem cells

Biochem Biophys Res Commun. 2016 Jun 10;474(4):691-695. doi: 10.1016/j.bbrc.2016.05.010. Epub 2016 May 3.

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.

Keywords: Benzene; Environmental epigenetics; Hematopoietic stem cells; Hydroquinone; Leukemia; Retrotransposon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • DNA / genetics*
  • DNA Methylation / drug effects
  • DNA Methylation / genetics*
  • Dose-Response Relationship, Drug
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / physiology*
  • Humans
  • Hydroquinones / administration & dosage*
  • Leukemia / genetics*
  • Retroelements / drug effects
  • Retroelements / genetics*
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • Hydroquinones
  • Retroelements
  • DNA
  • hydroquinone