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Human DNA damage by the synergistic action of 4-aminobiphenyl and nitric oxide: An immunochemical study.

Authors :
Moinuddin
Dixit, Kiran
Ahmad, Saheem
Shahab, Uzma
Habib, Safia
Naim, Mohammad
Alam, Khursheed
Ali, Asif
Source :
Environmental Toxicology; May2014, Vol. 29 Issue 5, p568-576, 9p
Publication Year :
2014

Abstract

4-Aminobiphenyl (4-ABP), an aromatic amine is a major environmental carcinogen found mainly in cigarette smoke. It has been vastly implicated in mutagenesis and cancer development. In this study, commercially available human placental DNA was exposed to 4-ABP (1.3 mM) in presence of sodium nitroprusside (SNP; 8 mM) at 37°C for 3 h. The 4-ABP + SNP-mediated structural changes in human DNA were studied by ultraviolet, circular dichroism and fluorescence spectroscopy, thermal melting profile, agarose gel electrophoresis, and nuclease S1 digestibility assay. Spectroscopical analysis and melting temperature studies suggest structural perturbations in the DNA as a result of modification. This might be due to generation of single-stranded regions and destabilization of hydrogen bonds. Modification was also visualized in agarose gel electrophoresis. Furthermore, nuclease S1 digestibility confirmed the generation of single strand breaks. Rabbits challenged with 4-ABP-SNP-modified human DNA-induced high-titer immunogen-specific antibodies, which showed Cross-reaction with modified/unmodified DNA bases and ss-DNA in competitive inhibition assay. The immunogen specificity of induced antibodies against 4-ABP-SNP-modified human DNA was further confirmed in gel retardation assay. It may be concluded that induction of anti-modified DNA antibodies could be due to perturbation in the DNA structure and its subsequent recognition by immunoregulatory cells as a foreign molecule. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 568-576, 2014. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
15204081
Volume :
29
Issue :
5
Database :
Complementary Index
Journal :
Environmental Toxicology
Publication Type :
Academic Journal
Accession number :
95425760
Full Text :
https://doi.org/10.1002/tox.21782