Generation of Autoantibodies in Metal-catalyzed Oxidatively Damaged DNA in Various Cancer Subjects
- Authors: Ahmad S.1, Alshammari Q.2, Rafi Z.3, Rehman S.4, Khan M.5, Faisal M.6, Alatar A.6
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Affiliations:
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Hail
- Diagnostic Radiology Department, College of Applied Medical Sciences,, University of Hail
- Department of Biosciences, Integral University
- Department of Biochemistry, S.S. Faculty of Science, Mohammad Ali Jauhar University
- Department of Biotechnology, School of Applied & Life Science (SALS), Uttaranchal University
- Department of Botany & Microbiology, College of Science,, King Saud University
- Issue: Vol 31, No 5 (2024)
- Pages: 640-648
- Section: Anti-Infectives and Infectious Diseases
- URL: https://rjmseer.com/0929-8673/article/view/645167
- DOI: https://doi.org/10.2174/0929867330666230503143133
- ID: 645167
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Abstract
Background:Free radicals exist as unstable and highly reactive substances, occurring both in and outside the body. Free radicals are labeled as electron-hungry molecules formed from metabolism and endogenous burning of oxygen. They are transported in cells, upsetting the arrangement of molecules and instigating cellular injury. Hydroxyl radical (OH) is one of the highly reactive free radicals, which damages the biomolecules in its close vicinity.
Methods:In the present study, DNA was modified by the hydroxyl radical generated via the Fenton reaction. The OH-oxidized/-modified DNA (Ox-DNA) was characterized by UV-visible and fluorescence spectroscopy. Thermal denaturation was performed to reveal the susceptibility of modified DNA toward heat. The role of Ox-DNA was also established in probing the presence of autoantibodies against Ox-DNA in the sera of cancer patients by direct binding ELISA. The specificity of autoantibodies was also checked by inhibition ELISA.
Results:In biophysical characterization, an increase in hyperchromicity and relative reduction of fluorescence intensity for Ox-DNA was reported compared to the native DNA analog. A thermal denaturation study revealed that Ox-DNA was highly susceptible to heat in comparison to the native conformers. The direct binding ELISA showed the prevalence of autoantibodies from cancer patient sera separated for immunoassay detection against the Ox-DNA. The generated autoantibodies against the Ox-DNA were detected as highly specific against bladder, head, neck, and lung cancer, which was further confirmed by the inhibition ELISA for the serum and IgG antibodies.
Conclusion:The generated neoepitopes on DNA molecules are recognized as nonself by the immune system, which leads to the formation of autoantibodies in cancer patients. Therefore, our study confirmed that oxidative stress plays a role in the structural perturbation of DNA and makes it immunogenic.
About the authors
Saheem Ahmad
Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Hail
Author for correspondence.
Email: info@benthamscience.net
Qurain Alshammari
Diagnostic Radiology Department, College of Applied Medical Sciences,, University of Hail
Email: info@benthamscience.net
Zeeshan Rafi
Department of Biosciences, Integral University
Email: info@benthamscience.net
Shahnawaz Rehman
Department of Biochemistry, S.S. Faculty of Science, Mohammad Ali Jauhar University
Email: info@benthamscience.net
Mohd. Khan
Department of Biotechnology, School of Applied & Life Science (SALS), Uttaranchal University
Email: info@benthamscience.net
Mohd. Faisal
Department of Botany & Microbiology, College of Science,, King Saud University
Email: info@benthamscience.net
Abdulrahman Alatar
Department of Botany & Microbiology, College of Science,, King Saud University
Email: info@benthamscience.net
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