Influences of polycyclic aromatic hydrocarbon on the epigenome toxicity and its applicability in human health risk assessment

Durgesh Nandini Das, Nathan Ravi

Research output: Contribution to journalReview articlepeer-review

Abstract

The existence of polycyclic aromatic hydrocarbons (PAHs) in ambient air is an escalating concern worldwide because of their ability to cause cancer and induce permanent changes in the genetic material. Growing evidence implies that during early life-sensitive stages, the risk of progression of acute and chronic diseases depends on epigenetic changes initiated by the influence of environmental cues. Several reports deciphered the relationship between exposure to environmental chemicals and epigenetics, and have known toxicants that alter the epigenetic states. Amongst PAHs, benzo[a]pyrene (B[a]P) is accepted as a group 1 cancer-causing agent by the International Agency for the Research on Cancer (IARC). B[a]P is a well-studied pro-carcinogen that is metabolically activated by the aryl hydrocarbon receptor (AhR)/cytochrome P450 pathway. Cytochrome P450 plays a pivotal role in the stimulation step, which is essential for DNA adduct formation. Accruing evidence suggests that epigenetic alterations assume a fundamental part in PAH-promoted carcinogenesis. This interaction between PAHs and epigenetic factors results in an altered profile of these marks, globally and locus-specific. Some of the epigenetic changes due to exposure to PAHs lead to increased disease susceptibility and progression. It is well understood that exposure to environmental carcinogens, such as PAH triggers disease pathways through changes in the genome. Several evidence reported due to the epigenome-wide association studies, that early life adverse environmental events may trigger widespread and persistent variations in transcriptional profiling. Moreover, these variations respond to DNA damage and/or a consequence of epigenetic modifications that need further investigation. Growing evidence has associated PAHs with epigenetic variations involving alterations in DNA methylation, histone modification, and micro RNA (miRNA) regulation. Epigenetic alterations to PAH exposure were related to chronic diseases, such as pulmonary disease, cardiovascular disease, endocrine disruptor, nervous system disorder, and cancer. This hormetic response gives a novel perception concerning the toxicity of PAHs and the biological reaction that may be a distinct reliance on exposure. This review sheds light on understanding the latest evidence about how PAHs can alter epigenetic patterns and human health. In conclusion, as several epigenetic change mechanisms remain unclear yet, further analyses derived from PAHs exposure must be performed to find new targets and disease biomarkers. In spite of the current limitations, numerous evidence supports the perception that epigenetics grips substantial potential for advancing our knowledge about the molecular mechanisms of environmental toxicants, also for predicting health-associated risks due to environmental circumstances exposure and individual susceptibility.

Original languageEnglish
Article number113677
JournalEnvironmental Research
Volume213
DOIs
StatePublished - Oct 2022

Keywords

  • Aryl hydrocarbon receptor
  • Benzo[a]pyrene
  • Carcinogenesis
  • Cytochrome P450
  • DNA adduct
  • DNA methylation
  • Epidemiology study
  • Histone modification
  • Micro-RNA
  • Polycyclic aromatic hydrocarbons

Fingerprint

Dive into the research topics of 'Influences of polycyclic aromatic hydrocarbon on the epigenome toxicity and its applicability in human health risk assessment'. Together they form a unique fingerprint.

Cite this