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http://hdl.handle.net/10603/13196
Title: | Immunochemical studies on human DNA damaged by n-hydroxy-4-acetylaminobiphenyl |
Researcher: | Uzma, Shahab |
Guide(s): | Moinuddin |
Keywords: | Biochemistry |
Upload Date: | 25-Nov-2013 |
University: | Aligarh Muslim University |
Completed Date: | 2011 |
Abstract: | 4-Aminobiphenyl (4-ABP) and several other related arylamines have been shown to be causally involved in the induction of human urinary bladder cancers. ABP induces a wide spectrum of tumors in a number of experimental animals. Arylamines, including ABP, were earlier used in chemical industries and are present in cigarette smoke and in other sources like hair dye, combustion of fossil fuels, rubber, coal, textile and printing industries. Hemoglobin-ABP adducts have been detected in the blood of smokers as well as non-smokers, although at much higher levels among smokers, who show an increased risk of bladder cancer. Thus, ABP and related aryl and heterocyclic amines represent an important class of environmental mutagens. The genotoxic and carcinogenic effects are exhibited when ABP is metabolically converted to a reactive electrophile, the aryl nitrenium ions, which subsequently binds to DNA. The various metabolic activation pathways that generate reactive electrophiles from arylamines or amides have been extensively studied in experimental animals. The activation of arylamines in general involves N-oxidation by hepatic enzymes followed by conjugation with acetate, sulfate, or glucuronate. In bladder carcinogenesis, the N-glucuronides formed by hepatic metabolism are postulated to be transported to the urinary bladder where they are hydrolyzed to the Nhydroxy derivatives. Under the acidic conditions of urine, the latter are thought to generate the aryl nitrenium ions that interact with critical cellular nucleophiles to initiate neoplasia. Alternatively, the procarcinogens or their proximate metabolites, Nhydroxy metabolites, namely N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP) and N-hydroxy-4-aminobiphenyl (N-OH-ABP) could be activated by the enzyme systems that are present in the urothelium. The N-hydroxyarylamines can then be converted to arylnitrenium ions through the putative intermediate. These electrophilic nitrenium ions interact with DNA to form covalent DNA adducts, thereby exerting their newlinegenotoxic effects. |
Pagination: | 171p. |
URI: | http://hdl.handle.net/10603/13196 |
Appears in Departments: | Department of Bio-Chemistry |
Files in This Item:
File | Description | Size | Format | |
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01_title.pdf | Attached File | 26.73 kB | Adobe PDF | View/Open |
02_certificate.pdf | 198.06 kB | Adobe PDF | View/Open | |
03_dedication.pdf | 1.88 MB | Adobe PDF | View/Open | |
04_acknowledgements.pdf | 26.18 kB | Adobe PDF | View/Open | |
05_contents.pdf | 9.36 kB | Adobe PDF | View/Open | |
06_abstract.pdf | 133.1 kB | Adobe PDF | View/Open | |
07_list of figures.pdf | 34.44 kB | Adobe PDF | View/Open | |
08_list of tables.pdf | 13.83 kB | Adobe PDF | View/Open | |
09_abbreviations.pdf | 45.92 kB | Adobe PDF | View/Open | |
10_chapter 1.pdf | 534.02 kB | Adobe PDF | View/Open | |
11_chapter 2.pdf | 217.57 kB | Adobe PDF | View/Open | |
12_chapter 3.pdf | 2.75 MB | Adobe PDF | View/Open | |
13_chapter 4.pdf | 163.07 kB | Adobe PDF | View/Open | |
14_references.pdf | 153.71 kB | Adobe PDF | View/Open |
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