title: Epigenetic factors in cancer risk: effect of chemical carcinogens on global DNA methylation pattern in human TK6 cells.
abstract: In the current study, we assessed the global DNA methylation changes in human lymphoblastoid (TK6) cells in vitro in response to 5 direct and 10 indirect-acting genotoxic agents. TK6 cells were exposed to the selected agents for 24 h in the presence and/or absence of S9 metabolic mix. Liquid chromatography-mass spectrometry was used for quantitative profiling of 5-methyl-2'-deoxycytidine. The effect of exposure on 5-methyl-2'-deoxycytidine between control and exposed cultures was assessed by applying the marginal model with correlated residuals on % global DNA methylation data. We reported the induction of global DNA hypomethylation in TK6 cells in response to S9 metabolic mix, under the current experimental settings. Benzene, hydroquinone, styrene, carbon tetrachloride and trichloroethylene induced global DNA hypomethylation in TK6 cells. Furthermore, we showed that dose did not have an effect on global DNA methylation in TK6 cells. In conclusion we report changes in global DNA methylation as an early event in response to agents traditionally considered as genotoxic.
authors.affiliation: Department of Occupational, Environmental and Insurance Medicine, Katholieke Universiteit Leuven, Leuven, Belgium. Tabish.Ali@med.kuleuven.be
authors.forename: Ali M
authors.initials: AM
authors.lastname: Tabish
authors.forename: Katrien
authors.initials: K
authors.lastname: Poels
authors.forename: Peter
authors.initials: P
authors.lastname: Hoet
authors.forename: Lode
authors.initials: L
authors.lastname: Godderis
mesh_terms: D002273:Carcinogens / Q000494:pharmacology* / Q000633:toxicity*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects* / Q000235:genetics; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009152:Mutagenicity Tests; D009369:Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors
chemical_list: D002273:Carcinogens; D003841:Deoxycytidine; C016569:5-methyldeoxycytidine