You have accessJournal of UrologyBladder Cancer: Basic Research (III)1 Apr 20131127 QUANTIFICATION OF MAJOR BLADDER CARCINOGENS - ACROLEIN AND AMINOBIPHENYL-INDUCED DNA ADDUCTS IN NORMAL HUMAN UROTHELIAL MUCOSA AND BLADDER TUMOR TISSUE Hyun-Wook Lee, Hsiang-Tsui Wang, Mao-wen Weng, Yan Liu, William C. Huang, Nicholas Donin, Xue-Ru Wu, Herbert Lepor, and Moon-shong Tang Hyun-Wook LeeHyun-Wook Lee New York, NY More articles by this author , Hsiang-Tsui WangHsiang-Tsui Wang New York, NY More articles by this author , Mao-wen WengMao-wen Weng New York, NY More articles by this author , Yan LiuYan Liu New York, NY More articles by this author , William C. HuangWilliam C. Huang New York, NY More articles by this author , Nicholas DoninNicholas Donin New York, NY More articles by this author , Xue-Ru WuXue-Ru Wu New York, NY More articles by this author , Herbert LeporHerbert Lepor New York, NY More articles by this author , and Moon-shong TangMoon-shong Tang New York, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.742AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Tobacco smoke (TS) is the major cause of bladder cancer (BC) in the US; BC incidence in tobacco smokers is 5-fold higher than in nonsmokers. TS contains 2 chemicals, 4-hydroxy-aminobiphenyl (ABP) and acrolein (Acr) that cause BC in animal models. Since ABP is a major cause of occupation-related BC and ABP-DNA adducts have been found in human bladder tissue, it has long been suspected that ABP is a major human bladder carcinogen in TS. While the amount of ABP in TS is minute (<5 ng/cigarette), the amount of Acr in TS is more than 100,000-fold higher than ABP. Moreover, Acr can form Acr-deoxyguanosine (Acr-dG) adducts that are mutagenic and can inhibit DNA repair and enhance DNA damage-induced mutations. Since inhaled Acr is excreted in urine, we hypothesize that Acr may initiate bladder carcinogenesis. As a first step to test this hypothesis we quantify Acr and ABP induced DNA adducts in normal human urothelium and in BC tissues. METHODS We developed 2 methods for quantification of Acr-dG and ABP-DNA adducts in human bladder tissues: 1) chemistry method using 32P post-labeling the adducted nucleotides followed by 2- and 4-dimensional thin layer chromatography and high performance liquid chromatography, and 2) immunochemical method using monoclonal antibody against Acr-dG adducts as first antibody and labeling the second antibody with quantum dot. We determined the levels of Acr-dG and ABP-DNA adducts in 20 normal human urothelial mucosa samples and in 10 BC samples. RESULTS Both methods can quantify Acr-dG and ABP-DNA adduct levels and yield comparable results. The immunochemical method is 40-fold more sensitive than the chemistry method. Acr-dG adduct levels are 20-100-fold higher than ABP-DNA adduct levels in both normal urothelium and BC tissues, and Acr-dG levels in BC tissues are 2-fold higher than in normal urothelium. CONCLUSIONS The levels of Acr-DNA adducts in normal human urothelium are 20-100 times higher than ABP-DNA adduct levels, and Acr-dG levels in BC tissues are 2 times higher than in normal urothelium. These results support the hypothesis that Acr is a major bladder carcinogen, and will have a major impact on bladder cancer risk assessment and design of new BC prevention strategies. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e460-e461 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hyun-Wook Lee New York, NY More articles by this author Hsiang-Tsui Wang New York, NY More articles by this author Mao-wen Weng New York, NY More articles by this author Yan Liu New York, NY More articles by this author William C. Huang New York, NY More articles by this author Nicholas Donin New York, NY More articles by this author Xue-Ru Wu New York, NY More articles by this author Herbert Lepor New York, NY More articles by this author Moon-shong Tang New York, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...
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