Differential crosstalk between global DNA methylation and metabolomics associated with cell type specific stress...

Area of Science:

• Toxicology
• Nanomaterial Science
• Epigenetics

Background:

• Multi-walled carbon nanotubes (MWCNT) are widely used but their toxicity mechanisms require detailed investigation.
• Cell specificity and the role of surface functionalization in MWCNT toxicity are not fully understood.

Purpose of the Study:

• To elucidate the comprehensive mechanisms of MWCNT-induced toxicity.
• To evaluate the impact of surface functionalization (hydroxylation/carboxylation) on MWCNT toxicity and cell specificity.
• To investigate intracellular uptake, toxicological endpoints, metabolomics, and DNA methylation.

Main Methods:

• In vitro exposure of human bronchial epithelial (BEAS-2B) and human hepatoma (HepG2) cell lines to pristine and functionalized MWCNT.
• Assessment of intracellular uptake using surface-enhanced Raman scattering and dark-field microscopy.
• Evaluation of toxicological endpoints, global metabolomics, and DNA methylation (DNMT3B-dependent).

Main Results:

• Surface functionalization significantly diminished the toxic potential of MWCNT compared to pristine counterparts.
• Functionalized MWCNT demonstrated intracellular uptake, unlike pristine MWCNT.
• MWCNT exposure induced cell-type and surface-functionalization-dependent alterations in stress responses, gene expression, metabolomics, and DNA methylation patterns.

Conclusions:

• Surface functionalization is a key factor in modulating MWCNT toxicity and cellular interactions.
• Differential metabolomic profiles and DNA methylation patterns underlie cell-type specificity and gene expression changes induced by MWCNT.
• Findings provide preliminary evidence for epigenetic modifications and metabolomics in MWCNT risk assessment.