Acrolein induced DNA damage, mutagenicity and effect on DNA repair

✍ Scribed by Moon-shong Tang; Hsiang-tsui Wang; Yu Hu; Wei-Sheng Chen; Makoto Akao; Zhaohui Feng; Wenwei Hu

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 426 KB
• Volume: 55
• Category: Article
• ISSN: 1613-4125
• DOI: 10.1002/mnfr.201100148

✦ Synopsis

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.