Basic studies on epigenetic carcinogenesis of low-dose exposure to 1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) in vitro

Renjie Wang, Yi Cui, Yi Xu, Joseph Irudayaraj

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere0172243
JournalPloS one
Volume12
Issue number2
DOIs
StatePublished - Feb 2017
Externally publishedYes

Fingerprint

Carbolines
carcinogenicity
DNA methylation
DNA Methylation
Epigenomics
epigenetics
carcinogenesis
Carcinogenesis
dosage
Methylation
tumor suppressor genes
HEK293 Cells
Cell proliferation
Tumor Suppressor Genes
methylation
Cell Movement
Toxicity
Tumors
cell proliferation
Genes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Basic studies on epigenetic carcinogenesis of low-dose exposure to 1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) in vitro. / Wang, Renjie; Cui, Yi; Xu, Yi; Irudayaraj, Joseph.

In: PloS one, Vol. 12, No. 2, e0172243, 02.2017.

Research output: Contribution to journalArticle

@article{3d5632d6fb72426c921e30432b79a28a,
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.",
author = "Renjie Wang and Yi Cui and Yi Xu and Joseph Irudayaraj",
year = "2017",
month = "2",
doi = "10.1371/journal.pone.0172243",
language = "English (US)",
volume = "12",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",

}

TY - JOUR

T1 - Basic studies on epigenetic carcinogenesis of low-dose exposure to 1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) in vitro

AU - Wang, Renjie

AU - Cui, Yi

AU - Xu, Yi

AU - Irudayaraj, Joseph

PY - 2017/2

Y1 - 2017/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85012910217&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85012910217&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0172243

DO - 10.1371/journal.pone.0172243

M3 - Article

C2 - 28199384

AN - SCOPUS:85012910217

VL - 12

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 2

M1 - e0172243

ER -