Affordable Access

deepdyve-link
Publisher Website

Mapping the Mitochondrial Regulation of Epigenetic Modifications in Association With Carcinogenic and Noncarcinogenic Polycyclic Aromatic Hydrocarbon Exposure.

Authors
  • Bhargava, Arpit1
  • Kumari, Roshani1
  • Khare, Surbhi1
  • Shandilya, Ruchita1
  • Gupta, Pushpendra Kumar1
  • Tiwari, Rajnarayan1
  • Rahman, Akhlaqur1
  • Chaudhury, Koel2
  • Goryacheva, Irina Yu3
  • Mishra, Pradyumna Kumar1
  • 1 Department of Molecular Biology, 275313ICMR-National Institute for Research in Environmental Health, Bhopal, India. , (India)
  • 2 School of Medical Science & Technology, 30133Indian Institute of Technology, Kharagpur, India. , (India)
  • 3 Department of General and Inorganic Chemistry, 64958Saratov State University, Saratov, Russia.
Type
Published Article
Journal
International journal of toxicology
Publication Date
Jan 01, 2020
Volume
39
Issue
5
Pages
465–476
Identifiers
DOI: 10.1177/1091581820932875
PMID: 32588678
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Polycyclic aromatic hydrocarbons (PAHs) refer to a ubiquitous group of anthropogenic air pollutants that are generated through incomplete carbon combustion. Although the immunotoxic nature of PAHs has been previously reported, the underlying molecular mechanisms of this effect are not fully understood. In the present study, we investigated the mitochondrial-mediated epigenetic regulation of 2 PAHs, carcinogenic (benzo[a]pyrene; BaP) and noncarcinogenic (anthracene [ANT]), in peripheral lymphocytes. While ANT exposure triggered mitochondrial oxidative damage, no appreciable epigenetic modifications were observed. On the other hand, exposure to BaP perturbed the mitochondrial redox machinery and initiated cascade of epigenetic modifications. Cells exposed to BaP showed prominent changes in the expression of mitochondrial microRNAs (miR-24, miR-34a, miR-150, and miR-155) and their respective gene targets (NF-κβ, MYC, and p53). The exposure of BaP also caused significant alterations in the expression of epigenetic modifiers (DNMT1, HDAC1, HDAC7, KDM3a, EZH2, and P300) and hypomethylation within nuclear and mitochondrial DNA. This further induced methylation of histone tails, which play a crucial role in the regulation of chromatin structure. Overall, our study provides novel mechanistic insights into the mitochondrial regulation of epigenetic modifications in association with PAH-induced immunotoxicity.

Report this publication

Statistics

Seen <100 times