Neo-epitopes on crotonaldehyde modified DNA preferably recognize circulating autoantibodies in cancer patients
DNA damage is one of the leading causes of various pathological conditions including carcinogenesis. Crotonaldehyde is a 4-carbon unsaturated bifunctional aldehyde which is found ubiquitously and produced both exogenously and endogenously. It reacts with deoxyguanosine and form adducts with DNA. These adducts were detected and found involved in tumor formation in rats treated with crotonaldehyde. In the present study, structural changes in DNA by crotonaldehyde were evaluated by Fourier transform infrared (FTIR) spectroscopy, differential scanning colorimetry (DSC), dynamic light scattering (DLS), high-performance liquid chromatography (HPLC), and atomic force microscopy (AFM). Enhanced binding was observed in cancer autoantibodies with the DNA modified by crotonaldehyde than the native counterpart. Immunological studies revealed enhanced binding of cancer autoantibodies with crotonaldehyde modified DNA, compared to the native form. Furthermore, lymphocyte DNA isolated from cancer patients demonstrated considerable recognition of anti-Cro-DNA IgG as compared to the DNA from healthy individuals. Therefore, we suggest that crotonaldehyde modified DNA presents unique epitopes, that may trigger autoantibody induction in cancer patients.
KeywordsHuman DNA Crotonaldehyde Crosslinking Neo-epitopes Cancer
One of the authors B. U. I. is thankful to University Grant Commission-Maulana Azad National Fellowship (UGC-MANF) for financial support as Senior Research Fellow (2011-12-MANF-MUS-UTT-24). Assistance from the Institution (AMU) as well as infrastructural support from DST-FIST to the department is duly acknowledged. The authors are grateful to Inderchand Rajgarhia and Sons Pvt. (India) Ltd for providing mica sheets.
Conflicts of interest
- 4.International Agency for Research on Cancer. Dry cleaning, some chlorinated solvents and other industrial chemicals, IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, IARC, Lyon. 1995; 63:373-91.Google Scholar
- 14.Zhang S, Villalta PW, Wang M, Hecht SS. Analysis of crotonaldehyde- and acetaldehyde-derived 1, N2-propanodeoxyguanosine adducts in DNA from human tissues using liquid chromatography electrospray ionization tandem mass spectrometry. Chem Res Toxicol. 2006;19:1386–92.CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Ali R, Alam K. Evaluation of antibodies against oxygen free radical modified DNA by ELISA. In: Armstrong D, editor. Methods in Molecular Biology: Oxidative Stress Biomarkers and Antioxidant Protocols, 1st ed. Totowa, NJ: Humana Press. 2002;186:171–81.Google Scholar
- 43.Moinuddin, Ali A. SLE anti-DNA autoantibodies binding estradiol albumin-DNA conjugate. Lupus. 1994;3:43–6.Google Scholar