Genotoxic effect of N-hydroxy-4-acetylaminobiphenyl on human DNA: implications in bladder cancer.

<h4>Background</h4>The interaction of environmental chemicals and their metabolites with biological macromolecules can result in cytotoxic and genotoxic effects. 4-Aminobiphenyl (4-ABP) and several other related arylamines have been shown to be causally involved in the induction of human...

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Autores principales:	Uzma Shahab, Moinuddin, Saheem Ahmad, Kiran Dixit, Safia Habib, Khursheed Alam, Asif Ali
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ed3b0ad8bc384c63b01618b7cd693a06
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spelling	oai:doaj.org-article:ed3b0ad8bc384c63b01618b7cd693a062021-11-18T07:59:17ZGenotoxic effect of N-hydroxy-4-acetylaminobiphenyl on human DNA: implications in bladder cancer.1932-620310.1371/journal.pone.0053205https://doaj.org/article/ed3b0ad8bc384c63b01618b7cd693a062013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23382838/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The interaction of environmental chemicals and their metabolites with biological macromolecules can result in cytotoxic and genotoxic effects. 4-Aminobiphenyl (4-ABP) and several other related arylamines have been shown to be causally involved in the induction of human urinary bladder cancers. The genotoxic and the carcinogenic effects of 4-ABP are exhibited only when it is metabolically converted to a reactive electrophile, the aryl nitrenium ions, which subsequently binds to DNA and induce lesions. Although several studies have reported the formation of 4-ABP-DNA adducts, no extensive work has been done to investigate the immunogenicity of 4-ABP-modified DNA and its possible involvement in the generation of antibodies in bladder cancer patients.<h4>Methodology/principal findings</h4>Human DNA was modified by N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP), a reactive metabolite of 4-ABP. Structural perturbations in the N-OH-AABP modified DNA were assessed by ultraviolet, fluorescence, and circular dichroic spectroscopy as well as by agarose gel electrophoresis. Genotoxicity of N-OH-AABP modified DNA was ascertained by comet assay. High performance liquid chromatography (HPLC) analysis of native and modified DNA samples confirmed the formation of N-(deoxyguanosine-8-yl)-4-aminobiphenyl (dG-C8-4ABP) in the N-OH-AABP damaged DNA. The experimentally induced antibodies against N-OH-AABP-modified DNA exhibited much better recognition of the DNA isolated from bladder cancer patients as compared to the DNA obtained from healthy individuals in competitive binding ELISA.<h4>Conclusions/significance</h4>This work shows epitope sharing between the DNA isolated from bladder cancer patients and the N-OH-AABP-modified DNA implicating the role of 4-ABP metabolites in the DNA damage and neo-antigenic epitope generation that could lead to the induction of antibodies in bladder cancer patients.Uzma ShahabMoinuddinSaheem AhmadKiran DixitSafia HabibKhursheed AlamAsif AliPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e53205 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Uzma Shahab Moinuddin Saheem Ahmad Kiran Dixit Safia Habib Khursheed Alam Asif Ali Genotoxic effect of N-hydroxy-4-acetylaminobiphenyl on human DNA: implications in bladder cancer.
description	<h4>Background</h4>The interaction of environmental chemicals and their metabolites with biological macromolecules can result in cytotoxic and genotoxic effects. 4-Aminobiphenyl (4-ABP) and several other related arylamines have been shown to be causally involved in the induction of human urinary bladder cancers. The genotoxic and the carcinogenic effects of 4-ABP are exhibited only when it is metabolically converted to a reactive electrophile, the aryl nitrenium ions, which subsequently binds to DNA and induce lesions. Although several studies have reported the formation of 4-ABP-DNA adducts, no extensive work has been done to investigate the immunogenicity of 4-ABP-modified DNA and its possible involvement in the generation of antibodies in bladder cancer patients.<h4>Methodology/principal findings</h4>Human DNA was modified by N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP), a reactive metabolite of 4-ABP. Structural perturbations in the N-OH-AABP modified DNA were assessed by ultraviolet, fluorescence, and circular dichroic spectroscopy as well as by agarose gel electrophoresis. Genotoxicity of N-OH-AABP modified DNA was ascertained by comet assay. High performance liquid chromatography (HPLC) analysis of native and modified DNA samples confirmed the formation of N-(deoxyguanosine-8-yl)-4-aminobiphenyl (dG-C8-4ABP) in the N-OH-AABP damaged DNA. The experimentally induced antibodies against N-OH-AABP-modified DNA exhibited much better recognition of the DNA isolated from bladder cancer patients as compared to the DNA obtained from healthy individuals in competitive binding ELISA.<h4>Conclusions/significance</h4>This work shows epitope sharing between the DNA isolated from bladder cancer patients and the N-OH-AABP-modified DNA implicating the role of 4-ABP metabolites in the DNA damage and neo-antigenic epitope generation that could lead to the induction of antibodies in bladder cancer patients.
format	article
author	Uzma Shahab Moinuddin Saheem Ahmad Kiran Dixit Safia Habib Khursheed Alam Asif Ali
author_facet	Uzma Shahab Moinuddin Saheem Ahmad Kiran Dixit Safia Habib Khursheed Alam Asif Ali
author_sort	Uzma Shahab
title	Genotoxic effect of N-hydroxy-4-acetylaminobiphenyl on human DNA: implications in bladder cancer.
title_short	Genotoxic effect of N-hydroxy-4-acetylaminobiphenyl on human DNA: implications in bladder cancer.
title_full	Genotoxic effect of N-hydroxy-4-acetylaminobiphenyl on human DNA: implications in bladder cancer.
title_fullStr	Genotoxic effect of N-hydroxy-4-acetylaminobiphenyl on human DNA: implications in bladder cancer.
title_full_unstemmed	Genotoxic effect of N-hydroxy-4-acetylaminobiphenyl on human DNA: implications in bladder cancer.
title_sort	genotoxic effect of n-hydroxy-4-acetylaminobiphenyl on human dna: implications in bladder cancer.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/ed3b0ad8bc384c63b01618b7cd693a06
work_keys_str_mv	AT uzmashahab genotoxiceffectofnhydroxy4acetylaminobiphenylonhumandnaimplicationsinbladdercancer AT moinuddin genotoxiceffectofnhydroxy4acetylaminobiphenylonhumandnaimplicationsinbladdercancer AT saheemahmad genotoxiceffectofnhydroxy4acetylaminobiphenylonhumandnaimplicationsinbladdercancer AT kirandixit genotoxiceffectofnhydroxy4acetylaminobiphenylonhumandnaimplicationsinbladdercancer AT safiahabib genotoxiceffectofnhydroxy4acetylaminobiphenylonhumandnaimplicationsinbladdercancer AT khursheedalam genotoxiceffectofnhydroxy4acetylaminobiphenylonhumandnaimplicationsinbladdercancer AT asifali genotoxiceffectofnhydroxy4acetylaminobiphenylonhumandnaimplicationsinbladdercancer
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Genotoxic effect of N-hydroxy-4-acetylaminobiphenyl on human DNA: implications in bladder cancer.

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