Key Genetic and Epigenetic Mechanisms in Chemical Carcinogenesis

Toxicol Sci. 2015 Nov;148(1):2-13. doi: 10.1093/toxsci/kfv165.

Abstract

DNA sequence and genetic factors alone cannot fully explain the many processes implicated in diseases initiation and development. It is now well understood that additional factors are involved in a final resulting phenotype. Epigenetic modifications, heritable changes not affecting the DNA sequence, are a key phenomenon at the basis of normal growth and differentiation. However, these can be defective leading to diseases, such as cancer. An increasing body of literature reports the environmental and occupational exposure to a mixture of natural and man-produced substances leading to epigenetic alterations. The identification of key genetic and/or epigenetic events involved in chemical carcinogenesis is an important step towards the discovery of biomarkers that can be used to evaluate the exposure, predict biological effects, and prevent adverse health consequences. Here, we focus on epidemiological studies to review the most recent advances in understanding genetic and epigenetic factors in relation to particulate matter, benzene and polycyclic aromatic hydrocarbons exposure.

Keywords: DNA methylation; benzene; gene expression/regulation; genetic polymorphisms; microRNA; particulate matter; polycyclic aromatic hydrocarbons.

Publication types

  • Review

MeSH terms

  • Animals
  • Benzene / toxicity
  • Biomarkers / metabolism
  • Carcinogenesis / chemically induced*
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Carcinogens / toxicity
  • Carcinogens, Environmental / toxicity*
  • DNA Methylation / drug effects
  • Environmental Exposure / adverse effects*
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene-Environment Interaction*
  • Genetic Predisposition to Disease
  • Humans
  • Models, Genetic*
  • Neoplasms / chemically induced*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Occupational Exposure / adverse effects
  • Particulate Matter / toxicity
  • Polycyclic Aromatic Hydrocarbons / toxicity
  • Polymorphism, Genetic
  • RNA Interference / drug effects

Substances

  • Biomarkers
  • Carcinogens
  • Carcinogens, Environmental
  • Particulate Matter
  • Polycyclic Aromatic Hydrocarbons
  • Benzene