title: Acrolein induced DNA damage, mutagenicity and effect on DNA repair.
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.
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo Park, NY 10967, USA. moon-shong.tang@nyumc.org
authors.forename: Moon-shong
authors.initials: MS
authors.lastname: Tang
authors.forename: Hsiang-tsui
authors.initials: HT
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Hu
authors.forename: Wei-Sheng
authors.initials: WS
authors.lastname: Chen
authors.forename: Makoto
authors.initials: M
authors.lastname: Akao
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Feng
authors.forename: Wenwei
authors.initials: W
authors.lastname: Hu
mesh_terms: D000171:Acrolein / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000378:metabolism; D018736:DNA Adducts / Q000737:chemistry; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D015227:Lipid Peroxidation; D008175:Lung Neoplasms / Q000235:genetics; D009152:Mutagenicity Tests; D009154:Mutation; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000209:etiology
chemical_list: D002273:Carcinogens; D018736:DNA Adducts; D016159:Tumor Suppressor Protein p53; D000171:Acrolein