Epigenetic Modifications in Chemical and Physical Carcinogenesis: From Mechanisms to Preventive Strategies

Abstract

This paper discusses the ways in which chemical and physical carcinogens remodel the epigenome to start, foster and advance cancer. The background integrates evidence that DNA methylation drift, histone-code disruption, non-coding RNA reprogramming, and 3D chromatin remodeling are early, reversible processes meditating the connection between exposure and altered gene expression, genomic instability, and development of malignant phenotypes. The aim is three-fold: (i) to identify exposure-dependent epigenetic marks of interest to key agents (e.g., PAHs, nitrosamines, heavy metals, ionizing/ UV radiation); (ii) to benchmark dose, timing, and tissue context with pathways of interest (DNA repair, oxidative stress, apoptosis, immune evasion); and (iii) to assess epigenetically-grounded preventive approaches that restore epigenetic homeostasis. In such experiments, we anticipate a unified framework to be derived regarding exposure-agnostic versus exposure-specific marks, sentinel loci and chromatin domains having high predictability regarding early detection, and evaluation of interventions including dietary consumption of methyl donors, HDAC/DNMT inhibitors at regulatory doses, circadian timing reset, and physically-induced epigenetic resilience. The paper envisages submitting a translational pipeline of exposure assessment, a liquid-biopsy epigenomics, and a risk-adapted prevention trial. Together it contends that high-resolution epigenetic mapping will enable heterogeneous exposures to be translated into prevention targets.