TY - JOUR
T1 - Differential crosstalk between global DNA methylation and metabolomics associated with cell type specific stress response by pristine and functionalized MWCNT
AU - Chatterjee, Nivedita
AU - Yang, Jisu
AU - Yoon, Dahye
AU - Kim, Suhkmann
AU - Joo, Sang Woo
AU - Choi, Jinhee
N1 - Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2017/1/1
Y1 - 2017/1/1
N2 - The present study endeavored to evaluate the comprehensive mechanisms of MWCNT-induced toxicity with particular emphasis on understanding cell specificity in relation to surface functionalization of MWCNT. Following treatment with differentially functionalized (hydroxylation/carboxylation) MWCNT on human bronchial epithelial (BEAS-2B) and human hepatoma (HepG2) cell lines, intracellular uptake, various toxicological end points, global metabolomics profiling and DNA methylation were evaluated. Herein, the comparative in vitro studies ascertained that surface functionalization diminished the toxic potentiality of MWCNT in respect of their pristine counterpart. The surface enhanced Raman scattering with dark-field microscopy attested the intracellular uptake of functionalized-MWCNT, but not the pristine one. The MWCNT's exposure caused alterations in stress responses (oxidative stress, inflammation, profibrosis, DNA damage-repair), differential mode of gene expressions, global metabolomics and DNA methylation status (DNMT3B dependent hypo-methylation in BEAS-2B cells and hyper-methylation in HepG2 cells) in a cell type specific and surface functionalization dependent manner. The alterations in particular metabolites (choline, betaine, succinate etc.) and distinct DNA methylation crosstalk patterns are the possible underlying mechanisms of differential mode of gene expressions and cell type specificity of MWCNT. This study provides preliminary evidence of epigenetic modifications and global metabolomics profiling which might be translated for risk assessment of MWCNT.
AB - The present study endeavored to evaluate the comprehensive mechanisms of MWCNT-induced toxicity with particular emphasis on understanding cell specificity in relation to surface functionalization of MWCNT. Following treatment with differentially functionalized (hydroxylation/carboxylation) MWCNT on human bronchial epithelial (BEAS-2B) and human hepatoma (HepG2) cell lines, intracellular uptake, various toxicological end points, global metabolomics profiling and DNA methylation were evaluated. Herein, the comparative in vitro studies ascertained that surface functionalization diminished the toxic potentiality of MWCNT in respect of their pristine counterpart. The surface enhanced Raman scattering with dark-field microscopy attested the intracellular uptake of functionalized-MWCNT, but not the pristine one. The MWCNT's exposure caused alterations in stress responses (oxidative stress, inflammation, profibrosis, DNA damage-repair), differential mode of gene expressions, global metabolomics and DNA methylation status (DNMT3B dependent hypo-methylation in BEAS-2B cells and hyper-methylation in HepG2 cells) in a cell type specific and surface functionalization dependent manner. The alterations in particular metabolites (choline, betaine, succinate etc.) and distinct DNA methylation crosstalk patterns are the possible underlying mechanisms of differential mode of gene expressions and cell type specificity of MWCNT. This study provides preliminary evidence of epigenetic modifications and global metabolomics profiling which might be translated for risk assessment of MWCNT.
KW - DNA methylation
KW - In vitro cell type specificity
KW - MWCNT
KW - NMR metabolomics
KW - Surface functionalization
UR - http://www.scopus.com/inward/record.url?scp=85007312159&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2016.11.005
DO - 10.1016/j.biomaterials.2016.11.005
M3 - Article
C2 - 27914347
AN - SCOPUS:85007312159
SN - 0142-9612
VL - 115
SP - 167
EP - 180
JO - Biomaterials
JF - Biomaterials
ER -