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Review
. 2024 May 4:12:502-519.
doi: 10.1016/j.toxrep.2024.04.010. eCollection 2024 Jun.

Genetic and epigenetic modulations in toxicity: The two-sided roles of heavy metals and polycyclic aromatic hydrocarbons from the environment

Peter Ifeoluwa Adegbola  1 , Adewale Adetutu  2
Affiliations
Review

Genetic and epigenetic modulations in toxicity: The two-sided roles of heavy metals and polycyclic aromatic hydrocarbons from the environment

Peter Ifeoluwa Adegbola et al. Toxicol Rep. .

Abstract

This study emphasizes the importance of considering the metabolic and toxicity mechanisms of environmental concern chemicals in real-life exposure scenarios. Furthermore, environmental chemicals may require metabolic activation to become toxic, and competition for binding sites on receptors can affect the severity of toxicity. The multicomplex process of chemical toxicity is reflected in the activation of multiple pathways during toxicity of which AhR activation is major. Real-life exposure to a mixture of concern chemicals is common, and the composition of these chemicals determines the severity of toxicity. Nutritional essential elements can mitigate the toxicity of toxic heavy metals, while the types and ratio of composition of PAH can either increase or decrease toxicity. The epigenetic mechanisms of heavy metals and PAH toxicity involves either down-regulation or up-regulation of some non-coding RNAs (ncRNAs) whereas specific small RNAs (sRNAs) may have dual role depending on the tissue and circumstance of expression. Similarly, decrease DNA methylation and histone modification are major players in heavy metals and PAH mediated toxicity and FLT1 hypermethylation is a major process in PAH induced carcinogenesis. Overall, this review provides the understanding of the metabolism of environmental concern chemicals, emphasizing the importance of considering mixed compositions and real-life exposure scenarios in assessing their potential effects on human health and diseases development as well as the dual mechanism of toxicity via genetic or epigenetic axis.

Keywords: Epigenetics; Heavy metals; Metabolism; Mixed-exposure; PAH; Small RNAs.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

None
Graphical abstract
Fig. 1
Fig. 1
AhR mediated differentiation of cardiomyocytes.
Fig. 2
Fig. 2
Mechanism of PAH mediated inflammation via the MEKK Pathway.
Fig. 3
Fig. 3
Enrichment analysis of cell division, proliferation, apoptosis, inflammation, oxidative stress, metabolism, and xenobiotic stress response signatures .
Fig. 4
Fig. 4
Pathway illustrating the mechanism of toxicity of heavy metals and PAH.
See this image and copyright information in PMC

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