title: DNA Glycation from 3-Deoxyglucosone Leads to the Formation of AGEs: Potential Role in Cancer Auto-antibodies.
abstract: The non-enzymatic glycation reaction results in the generation of free radicals which play an important role in the pathophysiology of aging, diabetes, and cancer. 3-Deoxyglucosone (3-DG) is a dicarbonyl species which may lead to the formation of advanced glycation end products (AGEs). 3-DG also reacts with free amino group of nucleic acids resulting in the formation of DNA-AGEs. While the establishment of nucleoside AGEs has been revealed before, no extensive studies have been done to probe the role of 3-DG in the generation of immunogenicity and induction of cancer auto-antibodies. In this study, we report the immunogenicity of AGEs formed by 3-DG-Arg-Fe(3+) system. Spectroscopic analysis and melting temperature studies suggest structural perturbations in the DNA as a result of modification. Immunogenicity of native and 3-DG-Arg-Fe(3+) DNA was probed in female rabbits. The modified DNA was highly immunogenic eliciting high-titer immunogen-specific antibodies, while the unmodified form was almost non-immunogenic. We also report the presence of auto-antibodies against 3-DG-Arg-Fe(3+)-modified DNA in the sera of patients with different types of cancers. The glycoxidative lesions were also detected in the lymphocyte DNA isolated from selected cancer patients. The results show structural perturbations in 3-DG-Arg-Fe(3+)-DNA generating new epitopes that render the molecule immunogenic.
authors.affiliation: School of Biotechnology, Yeungnam University, Gyeongsan, Republic of Korea.
authors.forename: Jalaluddin M
authors.initials: JM
authors.lastname: Ashraf
authors.affiliation: Department of Biochemistry, King George's Medical University, Lucknow, U.P., India.
authors.forename: Uzma
authors.initials: U
authors.lastname: Shahab
authors.affiliation: King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Shams
authors.initials: S
authors.lastname: Tabrez
authors.affiliation: School of Biotechnology, Yeungnam University, Gyeongsan, Republic of Korea.
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: School of Biotechnology, Yeungnam University, Gyeongsan, Republic of Korea. inhochoi@ynu.ac.kr.
authors.forename: Inho
authors.initials: I
authors.lastname: Choi
authors.affiliation: Department of Bioengineering, Integral University, Lucknow, U.P., India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Aslam Yusuf
authors.affiliation: Department of Bio-Sciences, Integral University, Lucknow, U.P., India. ahmadsaheem@gmail.com.
authors.forename: Saheem
authors.initials: S
authors.lastname: Ahmad
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000276:immunology* / Q000378:metabolism; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D017127:Glycation End Products, Advanced / Q000276:immunology*; D006801:Humans; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism; D011817:Rabbits
chemical_list: D000912:Antibodies, Neoplasm; D001323:Autoantibodies; D004273:DNA, Neoplasm; D017127:Glycation End Products, Advanced; D003847:Deoxyglucose; C016350:3-deoxyglucosone
keywords: 3-Deoxyglucosone (3-DG); Advanced glycation end products (AGEs); Cancer; Free radicals (hydroxyl and superoxide anions); Glycation; Immunogenicity