Acrolein induced DNA damage, mutagenicity and effect on DNA repair

Mol Nutr Food Res. 2011 Sep;55(9):1291-300. doi: 10.1002/mnfr.201100148. Epub 2011 Jun 29.

Abstract

Acrolein (Acr) is a ubiquitous environmental contaminant; it also can be generated endogenously by lipid peroxidation. Acr contains a carbonyl group and an olefinic double bond; it can react with many cellular molecules including amino acids, proteins and nucleic acids. In this review article we focus on updating information regarding: (i) Acr-induced DNA damage and methods of detection, (ii) repair of Acr-DNA damage, (iii) mutagenicity of Acr-DNA adducts, (iv) sequence specificity and methylation effect on Acr-DNA adduct formation and (v) the role of Acr in human cancer. We have found that Acr can inhibit DNA repair and induces mutagenic Acr-dG adducts and that the binding spectrum of Acr in the p53 gene in normal human bronchial epithelial cells is similar to the p53 mutational spectrum in lung cancer. Since Acr-DNA adduct has been identified in human lung tissue and Acr causes bladder cancer in human and rat models, we conclude that Acr is a major lung and bladder carcinogen, and its carcinogenicity arises via induction of DNA damage and inhibition of DNA repair.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Acrolein / chemistry
  • Acrolein / metabolism*
  • Acrolein / toxicity*
  • Animals
  • Carcinogenicity Tests
  • Carcinogens / metabolism
  • DNA Adducts / chemistry
  • DNA Damage*
  • DNA Repair*
  • Humans
  • Lipid Peroxidation
  • Lung Neoplasms / genetics
  • Mutagenicity Tests
  • Mutation
  • Rats
  • Tumor Suppressor Protein p53 / genetics
  • Urinary Bladder Neoplasms / etiology

Substances

  • Carcinogens
  • DNA Adducts
  • Tumor Suppressor Protein p53
  • Acrolein