Title: Acrolein induced DNA damage, mutagenicity and effect on DNA repair.
Authors: Tang, Moon-shong; Wang, Hsiang-tsui; Hu, Yu; Chen, Wei-Sheng; Akao, Makoto; Feng, Zhaohui; Hu, Wenwei
Published In Mol Nutr Food Res, (2011 Sep)
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.
PubMed ID: 21714128
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