Genotoxicity and immunogenicity of crotonaldehyde modified human DNA

DNA damage plays an important role in mutagenesis, carcinogenesis, aging and several other pathophysiological conditions. Crotonaldehyde is a four carbon unsaturated bifunctional aldehyde produced both exogenously and endogenously. It reacts with deoxyguanosine in DNA to form adducts. In this study, crotonaldehyde induced modifications of human DNA were evaluated by various physicochemical techniques. Crosslinking of DNA was evident by agarose gel electrophoresis of S1 nuclease digested DNA, hydroxyapatite chromatography and comet assay. The crotonaldehyde modified DNA induced high titer antibodies in experimental animals which showed high specificity towards the immunogen. Spectroscopic studies revealed structural alterations in the DNA molecule upon crotonaldehyde treatment which result in the generation of neoepitopes and enhanced immunogenicity. The possible role of crotonaldehyde-modified DNA in cancer has been suggested.