Carcinogens and DNA damage

Biochem Soc Trans. 2018 Oct 19;46(5):1213-1224. doi: 10.1042/BST20180519. Epub 2018 Oct 3.

Abstract

Humans are variously and continuously exposed to a wide range of different DNA-damaging agents, some of which are classed as carcinogens. DNA damage can arise from exposure to exogenous agents, but damage from endogenous processes is probably far more prevalent. That said, epidemiological studies of migrant populations from regions of low cancer risk to high cancer risk countries point to a role for environmental and/or lifestyle factors playing a pivotal part in cancer aetiology. One might reasonably surmise from this that carcinogens found in our environment or diet are culpable. Exposure to carcinogens is associated with various forms of DNA damage such as single-stand breaks, double-strand breaks, covalently bound chemical DNA adducts, oxidative-induced lesions and DNA-DNA or DNA-protein cross-links. This review predominantly concentrates on DNA damage induced by the following carcinogens: polycyclic aromatic hydrocarbons, heterocyclic aromatic amines, mycotoxins, ultraviolet light, ionising radiation, aristolochic acid, nitrosamines and particulate matter. Additionally, we allude to some of the cancer types where there is molecular epidemiological evidence that these agents are aetiological risk factors. The complex role that carcinogens play in the pathophysiology of cancer development remains obscure, but DNA damage remains pivotal to this process.

Keywords: DNA damage; bioactivation; cancer; carcinogens.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amines / adverse effects
  • Animals
  • Aristolochic Acids / adverse effects
  • Benzo(a)pyrene / adverse effects
  • Carcinogens / chemistry*
  • Cross-Linking Reagents / chemistry
  • DNA
  • DNA Damage*
  • DNA Repair
  • Diet
  • Female
  • Humans
  • Inflammation
  • Lung Neoplasms / chemically induced
  • Lung Neoplasms / genetics
  • Male
  • Neoplasms / chemically induced
  • Neoplasms / genetics
  • Oxidative Stress
  • Polycyclic Aromatic Hydrocarbons / adverse effects*
  • Prostatic Neoplasms / chemically induced
  • Prostatic Neoplasms / genetics
  • Smoking / adverse effects
  • Ultraviolet Rays / adverse effects
  • Urinary Bladder Neoplasms / chemically induced
  • Urinary Bladder Neoplasms / genetics

Substances

  • Amines
  • Aristolochic Acids
  • Carcinogens
  • Cross-Linking Reagents
  • Polycyclic Aromatic Hydrocarbons
  • Benzo(a)pyrene
  • DNA
  • aristolochic acid I