Environmental Chemical Exposure and the Human Epitranscriptome: Toxicant Classes, Detection Tools, and Biomarker Potential

Abstract

Gene expression is no longer thought to be governed by DNA sequence and chromatin state alone. Over the last decade, chemical marks written directly onto RNA N6-methyladenosine (m6A), 5-methylcytosine (m5C), and pseudo uridine (Ψ) chief among them have emerged as a fast, reversible layer of regulation that shapes how efficiently a transcript is translated, how long it survives, and where it ends up inside the cell. Because these marks are added and removed by a finite set of enzymes that are themselves sensitive to the chemical environment of the cell, they turn out to be unusually good sensors of exposure to outside toxicants. This review draws together recent, largely 2022-2026 primary literature on how specific classes of environmental chemicals arsenic, chromium and cadmium, combustion-derived particulate matter, and the endocrine disruptor bisphenol A perturb the Epitranscriptome, and what this means for lung, metabolic and reproductive disease. It then turns to the practical side of the field: how nanopore sequencing and related platforms are being used to read these marks directly, why circulating tRNA fragments and m6A-tagged transcripts are being tested as blood-based exposure biomarkers, and how the same chemistry that toxicants disrupt has been engineered, in reverse, into a therapeutic tool  most visibly in pseudo uridine-modified mRNA vaccines. The aim is not to catalogue every known RNA mark, but to trace a workable line from mechanism to detectable, useful biomarker.