title: Basic studies on epigenetic carcinogenesis of low-dose exposure to 1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) in vitro.
abstract: 1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) has been widely studied as a neurotoxic substance, however, only few reports have explored its effect on carcinogenicity. Since the aberrant modification of DNA methylation occurs very early in almost all human cancers, the focus of this study is to assess the carcinogenicity of TaClo by characterizing alterations of the epigenetic state, specifically, DNA methylation, upon exposure to TaClo in a HEK 293 model cell line. Our results suggest that TaClo could induce global DNA hypomethylation and transcriptional repression of critical tumor suppressor genes by increasing their promoter methylation. Enhanced cell proliferation, migration and anchorage independent growth were observed in cells exposed to TaClo. Our study highlights the epigenetic toxicity of TaClo, which contributes to its carcinogenicity by altering the DNA methylation status.
authors.affiliation: College of Chemistry and Chemical Engineering, Chongqing University, Chongqing, China.|Department of Agricultural and Biological Engineering, Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, United States of America.|International R & D Center of Micro-Nano Systems and New Materials Technolog, Chongqing University, Chongqing, China.|Key disciplines laboratory of Novel Micro-Nano Devices and System Technology, Chongqing University, Chongqing, China.
authors.forename: Renjie
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Agricultural and Biological Engineering, Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, United States of America.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cui
authors.affiliation: College of Chemistry and Chemical Engineering, Chongqing University, Chongqing, China.|International R & D Center of Micro-Nano Systems and New Materials Technolog, Chongqing University, Chongqing, China.|Key disciplines laboratory of Novel Micro-Nano Devices and System Technology, Chongqing University, Chongqing, China.|Microsystem Research Center, School of Optoelectronic Engineering, Chongqing University, Chongqing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Agricultural and Biological Engineering, Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, United States of America.
authors.forename: Joseph
authors.initials: J
authors.lastname: Irudayaraj
mesh_terms: D002243:Carbolines / Q000633:toxicity*; D063646:Carcinogenesis / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D019175:DNA Methylation; D057890:Epigenomics; D057809:HEK293 Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D002243:Carbolines; D011518:Proto-Oncogene Proteins; C067372:1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline; D004247:DNA