Neo-epitopes on crotonaldehyde modified DNA preferably recognize circulating autoantibodies in cancer patients

Abstract

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.

Multi‐spectroscopic, thermodynamic and molecular docking studies to investigate the interaction of eplerenone with human serum albumin

“…In contrast to dynamic quenching, static quenching happens when molecules form a complex in the ground state. [ 54 ] And rising temperatures are likely to lower the quenching constant because the stability of ground state complexes is reduced by temperature. Therefore, the quenching rate constant would be smaller as the temperature increased in static quenching.…”